Phytochemistry xxx (2013) xxx–xxx
Contents lists available at SciVerse ScienceDirect
Phytochemistry
journal homepage: www.elsevier.com/locate/phytochem
Review
Sesquiterpenoids in subtribe Centaureinae (Cass.) Dumort
(tribe Cardueae, Asteraceae): Distribution, 13C NMR spectral
data and biological properties
Maurizio Bruno a,⇑, Svetlana Bancheva b, Sergio Rosselli a, Antonella Maggio a
a
b
STEBICEF, Section of Chemistry, University of Palermo, Viale delle Scienze, Parco d’Orleans II, 90128 Palermo, Italy
Institute of Biodiversity and Ecosystem Research, Bulgarian Academy of Sciences, Acad. G. Bonchev Str. 23, 1113 Sofia, Bulgaria
a r t i c l e
i n f o
Article history:
Received 15 October 2012
Received in revised form 5 July 2013
Available online xxxx
In memory of Professor Werner Herz,
Department of Chemistry, The Florida State
University, Tallahassee, FL, USA, who
dedicated his life to the chemistry of
sesquiterpenoids.
Keywords:
Centaureinae
Germacranes
Elemanes
Eudesmanes
Guiaianes
13
C NMR spectral data
Antimicrobial
Antiprotozoal
Anti-inflammatory
Antitumor and cytotoxic
Antiviral
Effects on insects
Effects on plants
a b s t r a c t
Asteraceae Bercht. & J. Presl is one of the biggest and most economically important plant families. The
taxonomy and phylogeny of Asteraceae is rather complex and according to the latest and most reliable
taxonomic classification of Panero & Funk, based on the analysis of nine chloroplast regions, the family
is divided into 12 subfamilies and 35 tribes. One of the largest tribes of Asteraceae is Cardueae Cass. with
four subtribes (Carlininae, Echinopinae, Carduinae and Centaureinae) and more than 2500 species. Susanna & Garcia-Jacas have organized the genera of Centaureinae (about 800 species) into seven informal
groups, which recent molecular studies have confirmed: 1. Basal genera; 2. Volutaria group; 3. Rhaponticum group; 4. Serratula group; 5. Carthamus group; 6. Crocodylium group; 7. Centaurea group.
This review summarizes reports on sesquiterpenoids from the Centaureinae subtribe of the Asteraceae
family, as well as the 13C NMR spectral data described in the literature.
It further reviews studies concerning the biological activities of these metabolites.
For this work, literature data on sesquiterpenes from the Centaureinae subtribe were retrieved with the
help of the SciFinder database and other similar data banks. All entries from 1958 until the end of 2011 were
considered. This review is addressed to scientists working in the metabolomics field such as chemists, botanists, etc., the spectroscopic data reported make this work a good tool for structural elucidation, the biological section gives useful information to those who wish to study the structure activity relationships.
Ó 2013 Elsevier Ltd. All rights reserved.
Contents
1.
2.
3.
4.
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Sesquiterpenes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2.1.
Germacranes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2.2.
Elemanes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2.3.
Eudesmanes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2.4.
Guaianes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2.5.
Others . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Chemotaxonomic remarks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Biological activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4.1.
Antimicrobial . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4.2.
Antiprotozoal . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4.3.
Anti-inflammatory. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4.4.
Antitumor and cytotoxic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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⇑ Corresponding author.
E-mail address: maurizio.bruno@unipa.it (M. Bruno).
0031-9422/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.phytochem.2013.07.002
Please cite this article in press as: Bruno, M., et al. Sesquiterpenoids in subtribe Centaureinae (Cass.) Dumort (tribe Cardueae, Asteraceae): Distribution, 13C
NMR spectral data and biological properties. Phytochemistry (2013), http://dx.doi.org/10.1016/j.phytochem.2013.07.002
2
M. Bruno et al. / Phytochemistry xxx (2013) xxx–xxx
5.
4.5.
Antiviral . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4.6.
Effects on insects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4.7.
Effects on plants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4.8.
Other activities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Conclusions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Appendix A. Supplementary data. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1. Introduction
Asteraceae Bercht. & J. Presl is one of the biggest (more than
23,000 currently accepted species spread across 1620 genera)
and most economically important plant families. In fact, many economically important weeds, for example hawkweeds (Hieracium
sp.), thistles (Cirsium sp., Carduus sp. and other representatives
from tribe Cardueae), yellow star thistle (Centaurea solstitialis L.)
and dandelion (Taraxacum officinale) belong to the Asteraceae. Sunflowers (Helianthus annuus) are grown for the oil in their seeds and
safflowers (Carthamus tinctorius) have been used for a long time as
a textile dye. Artichoke (Cynara cardunculus) is an example of a
crop plant belonging to this family, and many species are used as
flavor herbs (marigold, various daisies, fleabane, chrysanthemums,
dahlias, zinnias) or medicines (grindelia, echinacea, yarrow and
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00
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many others). Furthermore, pyrethrum daisies (Tanacetum coccineum) provide a popular and relatively bio-friendly insecticide (Smissen, 2003).
According to the last and most reliable taxonomic classification
of Panero and Funk (2002, 2008), based on analysis of nine chloroplast regions, the family is divided into 12 subfamilies and 35
tribes. One of the largest tribes of the Asteraceae is Cardueae Cass.
with four subtribes (Carlininae, Echinopinae, Carduinae and Centaureinae) and more than 2500 species. Subtribe Centaureinae
(about 800 species) is the most derived group and is characterized
by achenes with a lateral–adaxial insertion areole, a double pappus, and, with a few exceptions, unarmed leaves (Wagenitz and
Hellwig, 1996). Susanna and Garcia-Jacas (2007) have organized
the genera of Centaureinae into several informal groups, which recent molecular studies have confirmed as natural: 1. Basal genera;
Table 1
List of the studied Centaureinae taxa, divided into seven groups, proposed by Susanna and Garcia-Jacas.
Group 1
Basal genera
Group 2
Volutaria group
Group 3
Rhaponticum
group
Group 4
Serratula
group
Group 5
Carthamus
group
Group 6
Crocodylium
group
Group 7
Centaurea group
Aetheopappus (Cass.) Wagenitz & Hellwig
Acroptilon Cass.
Serratula
L. s.str.
Carthamus L.
Crocodylium
Vaill
Acrolophus Cass.
Amblyopogon (DC.) Wagenitz & Hellwig
Amberboa Vall.
(= Volutarella Cass.)
Cyanopsis Cass.
Cheirolophus Cass.
Goniocaulon Cass.
Crupina (Pers.) DC.
Karvandarina Rech. f
Czerniakowskya (Czerep.) Wagenitz & Hellwig
Heterolophus (Cass.) Wagenitz & Hellwig
Mantisalca Cass.
Plagiobasis Schrenk
Hyalinella (Tzvelev) Wagenitz & Hellwig
Russowia C.Winkl.
Odontolophoidei (Tzvelev) Wagenitz & Hellwig
Odontolophus (Cass.) Wag. et Hell.
Plectocephalus D.Don
Psephellus Cass.
Rhaponthicoides Vaill.
Sosnowskya (Takht.) Wagenitz & Hellwig
Stizolophus Cass.
Uralepis (DC.) Wagenitz & Hellwig
Xanthopsis (DC.) Wagenitz & Hellwig
Zoegea L.
Tricholepis DC.
Valutaria Cass.
Callicephalus C.A.
Mey
Centaurothamnus
Wagenitz & Dittrich
Leuzea DC.
Ochrocephala
Dittrich
Oligochaeta (DC) K.
Koch
Rhaponticum Vall.
Stemmacantha Cass.
Phonus Hill.
Aegialophila Boiss. & Heldr.
Carduncellus
Adans.
Femeniasia
Susanna
Calcitrapa Adans.
Centaurea L. s.str.
Chartolepis Cass.
Cnicus L.
Colymbada Hill
Corethropsis DC.
Cyanus Mill.
Grossheimia Sosn. & Takht.
Hymenocentron (Cass.) DC.
Jacea Mill.
Lepteranthus (DC.) DC.
Melanoloma Cass.
Mesocentron (Cass.) DC.
Microlophus (Cass.) DC.
Paraphysis (DC.) Wagenitz
Pectinastrum (Cass.) DC.
Phalolepis (Cass.) DC.
Plumosipappus (Czerep.)
Wagenitz
Pseudophaeopappus
Wagenitz
Pseudoseridia Wagenitz
Protocyanus Dobrocz.
Pteracantha Wagenitz
Ptosimopappus Boiss
Seridia Juss.
Seridioides DC.
Solstitiaria (Hill) Dobrocz.
Stephanochilus Coss. &
Durieu ex Benth. & Hook f.
Tetramorphaea (DC.) Boiss.
Triplocentron (Cass.) Spach
Wagenitzia Dostàl
Please cite this article in press as: Bruno, M., et al. Sesquiterpenoids in subtribe Centaureinae (Cass.) Dumort (tribe Cardueae, Asteraceae): Distribution, 13C
NMR spectral data and biological properties. Phytochemistry (2013), http://dx.doi.org/10.1016/j.phytochem.2013.07.002
3
M. Bruno et al. / Phytochemistry xxx (2013) xxx–xxx
2. Volutaria group; 3. Rhaponticum group; 4. Serratula group; 5.
Carthamus group; 6. Crocodylium group; 7. Centaurea group.
Basal genera – unarmed, annual to perennial herbs or shrubs
with solitary or corymbose capitula and double pappus; basal
chromosome numbers are usually x = 15.
Volutaria group – annual to perennial herbs with heterogamous
capitula and large and showy sterile radiant florets, with staminodes. Achenes have basal hilum and pappus of scales.
Rhaponticum group – unarmed perennial herbs with homogamous capitula and involucral bracts with very large, scarious
appendages, usually silvery-white; pappus is deciduous in a ring.
Serratula group – unarmed perennial herbs or shrubslets with
homogamous capitula and rudimentary appendages of bracts; achenes have basal hilum and double, easily deciduous pappus.
Carthamus group – annual or perennial herbs or shrublets, usually spiny with homogamous capitula and compressed, very hard
achenes, which have lateral hilum and double pappus.
Crocodylium group – annual or perennial herbs with fleshy,
glandular leaves and heterogamous capitula. All florets are with
many stalked glands and densely sericeous achenes.
Centaurea group – annual to perennial herbs or shrubs, usually
unarmed with heterogamous capitula and scarious involucral
bracts with a variable apical appendage, spiny or unarmed. Sterile
florets are radiant and showy; achenes – oblong, compressed with
lateral–adaxial insertion areole; pappus is double with pinnulate
or plumose outer bristles; basal chromosome numbers are x = 7,
8, 9, 10, 11, 12.
This review summarizes reports on sesquiterpenoids from the
Centaureinae subtribe of the Asteraceae family, as well as the 13C
NMR spectral data described in the literature.
According to the taxonomic scheme of Susanna and Garcia-Jacas (2007), the genera of subtribe Centaureinae are classified in seven groups. In Table 1 are listed the Centaureinae taxa, studied so
far by reason of their horology, karyology, genome size, DNA sequences, secondary metabolites, etc., as each taxon is arranged in
the appropriate group, following the classification mentioned
above. Some of the taxa in the Table have generic rank, while other
are subgenera, sections or synonyms. Our aim was to include in the
table all investigated Centaureinae taxa, but not to define their taxonomic rank. The Table contains a total of 72 taxonomic units.
The larger group is Centaurea (group 7) that comprises 32 taxa.
So far only 19 of the 72 representatives of the subtribe Centaureinae have been investigated for the occurrence of sesquiterpenes.
As we can see from the data here reported, not only most species but also the majority of the genera of the Centaureinae have
not yet been investigated for their sesquiterpene profile. The
authors hope that the compilation of data provided in the present
review will be helpful for people who plan to conduct further research on the Centaureinae, as they might provide first indications
on which compounds to expect in members of this subtribe not yet
investigated.
2. Sesquiterpenes
An extensive bibliographic search identified a total of 287 different sesquiterpenes from 218 species belonging to these 19 genera, among which the most intensively studied genera is Centaurea
(166 taxa). The analysis of the sesquiterpene structures of the subtribe Centaureinae allows us to point out some interesting chemotaxonomic structural features. Except for Centaurea calcitrapa, C.
solstitialis and Serratula latifolia, from which also compound 287
and two bisabolanes (285–286) were isolated, in all the other taxa
of Centaureinae only germacranes, elemanes, eudesmanes and
guaianes occur (Fig. 1). With the exception of three eudesmanes
(121, 122, 124) and four guaianes (280–283) isolated from S. latifo-
Fig. 1. Sesquiterpene skeletons.
lia and a few other eudesmanes occurring mainly in the genera
Cheirolophus and Phonus, all the sesquiterpenes have an a-oxygenated function at C-6 that, normally, is involved in the formation of
the C-6/C-12 c-lactone or, in some cases, is present as a free hydroxyl group. In contrast to other genera of the Asteraceae family,
belonging to different subtribes, the oxygenated function at C-8
is almost always a-orientated and, if present, the ester side chains
are often linked at this carbon, although it is possible to find the ester moiety in other positions. The 42 side chains present in the sesquiterpenoids from Centaurineae subtribe are depicted in Fig. 2
and Table 2 reports their 13C NMR spectroscopic data.
All the sesquiterpenes are listed with their semi-systematic and
trivial names and the genera and species, ordered alphabetically, in
which the compounds have been found. By far the most common
compound in the Centaureinae is cnicin (19) present in 83 taxa followed by the guaianolides cynaropicrin (162, 68 taxa), janerin
(208, 38 taxa) and chlorohyssopifolin A (224, 29 taxa).
2.1. Germacranes
The germacranes (68 compounds) detected in the subtribe
Centaureinae are listed in Table 3. Except for the heliangolides
59–68, present in Centaurea paui, Centaurea tweediei and Centaurea
sulphurea, and for a few C10(C14) enes all of them have a trans-C1(C-10)/trans-C-4 configuration. They are almost all C-6/C-12
olides with the typical exocyclic C-11/C-13 double bond or with
a C-11/C-13 dihydro moiety: only compounds 51 and 52 do not
have the lactone and the artemisiifolin derivatives 53–57 show a
C-8/C-12 olide ring. The presence of a primary alcohol or acetoxy
at C-15 and of the a-oxygenated function at C-8 are common features for almost all these germacranolides: in fact only few compounds have a C-15 methyl, mainly co-occurring with a C-4/C-5
epoxy ring, and just nine (1–3, 5, 28, 38, 48, 51, 52) are devoid of
the oxygenated function at C-8.
Table 4 reports a complete list of all 13C NMR spectroscopic data
quoted in the literature.
2.2. Elemanes
All
the
elemanes
(29
compounds,
Table
5)
have
an
a-orientated hydroxyl or ester at C-8 (except 87 which is devoid
of functionality) and an oxygenated function at C-15, mainly a
primary alcohol, but in three cases (compounds 70, 83, and
85) an aldehyde. In five cases (compounds 93–97) the C-6/C-
Please cite this article in press as: Bruno, M., et al. Sesquiterpenoids in subtribe Centaureinae (Cass.) Dumort (tribe Cardueae, Asteraceae): Distribution, 13C
NMR spectral data and biological properties. Phytochemistry (2013), http://dx.doi.org/10.1016/j.phytochem.2013.07.002
4
M. Bruno et al. / Phytochemistry xxx (2013) xxx–xxx
Fig. 2. Natural ester chains (acyl groups).
12 c-lactone is open showing a free a-hydroxyl at C-6 and a
carbomethoxy function at C-12. Only compound 92 has a C-8/
C-12 c-lactone. Table 6 reports a complete list of all
spectroscopic data quoted in the literature.
13
C NMR
Please cite this article in press as: Bruno, M., et al. Sesquiterpenoids in subtribe Centaureinae (Cass.) Dumort (tribe Cardueae, Asteraceae): Distribution, 13C
NMR spectral data and biological properties. Phytochemistry (2013), http://dx.doi.org/10.1016/j.phytochem.2013.07.002
5
M. Bruno et al. / Phytochemistry xxx (2013) xxx–xxx
Table 2
C NMR spectral data (CDCl3) of the side chains (S.C.) in sesquiterpenoids in the Subtribe Centaureinae.
13
S.C.
10
20
30 (70 )
40 (60 )
A
B
C
D
Ea
F
Fa
G
I
Ia
J
Ja
K
L
M
Nb
O
P
Q
R
S
T
U
V
W
Y
Z
ZAa
ZB
ZBc
ZCa
ZD
ZE
ZF
ZFa
ZG
ZHa
ZHd
ZHb
ZJ
ZK
ZL
ZM
ZN
ZOb
ZP
ZQ
170.5
20.8
176.0
166.1
169.7
174.8
174.5
175.1
165.2
165.7
164.3
167.0
169.9
170.1
173.1
173.9
173.1
175.0
34.1
136.2
45.9
41.9
42.2
42.4
139.0
141.0
135.0
nr
53.8
53.7
74.7
79.3
75.1
75.8
19.3
124.6
180.2
64.4
63.9
64.4
127.6
125.1
121.5
nr
52.8
52.9
51.2
51.8
50.9
68.5
18.5
18.4
15.2
13.5
14.9
13.5
62.3
61.8
62.2
nr
17.3
17.2
23.4
24.0
23.9
21.6
174.8
175.4
171.4
166.4
166.7
164.9
165.5
166.9
166.6
166.1
166.8
168.2
172.1
165.2
166.4
167.4
165.6
166.6
165.2
166.6
164.6
165.9
165.1
n.r.
165.9
167.1
164.7
166.8
76.0
41.3
43.3
126.9
128.4
115.1
127.8
136.6
130.2
135.0
126.9
128.9
38.4
112.4
131.7
132.1
131.4
142.3
141.9
142.4
138.3
131.5
130.6
n.r.
130.2
122.1
122.3
123.9
68.1
26.6
25.3
140.0
138.6
159.3
140.2
35.0
132.7
141.3
143.7
143.5
32.7
159.9
140.7
141.9
142.5
71.9
70.2
71.8
69.7
145.1
138.6
141.5
129.7
132.7
132.4
114.0
(124.1)
21.6
11.5
22.2
15.8
14.6
20.4
63.0
61.1
193.1
59.8
59.2
59.7
67.1
66.8
14.1
14.3
15.7
66.7
65.4
66.7
67.1
58.8
63.3
63.2
128.7
115.7
114.0
146.1
(111.7)
50
16.5
22.2
20.3
12.8
27.5
19.3
128.0
13.2
12.8
12.5
12.6
16.7
15.7
56.7
55.7
63.8
127.0
125.3
127.2
127.6
56.8
62.5
62.5
133.3
162.6
163.7
150.0
100
200
170.3
175.0
20.6
21.0
71.5
36.4
171.1
20.9
176.4
22.1
171.4
20.8
171.1
n.r.
20.5
20.8
55.6
56.0
51.8
300
131.0
400 ,800
116.2
500 ,700
130.9
600
156.2
Ref.
Cardona et al. (1997)
not reported in the literature
Bruno et al. (2011)
Bruno et al. (2011)
Khan et al. (2004a)
Bruno et al. (2011)
Khan et al. (2004a)
Marco et al. (1992)
Bruno et al. (2011)
Khan et al. (2005a)
Buděšinský and Šaman (1995)
Bruno et al. (2011)
Hamburger et al. (1993)
Hamburger et al. (1993)
Hamburger et al. (1993)
Dai et al. (2001)
Hamburger et al. (1993)
Bruno et al. (2005a)
not reported in the literature
Fernandez et al. (1989)
Buděšinský and Šaman (1995)
Buděšinský and Šaman (1995)
Buděšinský and Šaman (1995)
Bruno et al. (2011)
Buděšinský and Šaman (1995)
Buděšinský and Šaman (1995)
Buděšinský and Šaman (1995)
Youssef (1998)
Bruno et al. (2011)
Youssef and Frahm (1994a)
Youssef and Frahm (1994a)
Bruno et al. (2011)
Bruno et al. (2011)
Bruno et al. (2011)
Youssef (1998)
Buděšinský and Šaman (1995)
Csapi et al. (2010)
Barrero et al. (1997a)
Santos et al. (1995)
Karioti et al. (2002)
Buděšinský and Šaman (1995)
Saroglou et al. (2005)
Cardona et al. (1991)
Buděšinský and Šaman (1995)
Stevens et al. (1991)
Buděšinský and Šaman (1995)
Khan et al. (2008)
n.r. = not reported.
a
In MeOD.
b
In acetone-d6.
c
In CD2Cl2/DMSO-d6 7:1.
d
In DMSO-d6.
2.3. Eudesmanes
2.4. Guaianes
The eudesmane (44 compounds, Table 7) all have a trans fused
decalin moiety. Many of them carry a free b-oriented hydroxyl
group at C-1 and an aldehyde at C-4 that can be a or b oriented.
The stereochemistry of C-4 can easily be determined by 1H NMR
spectra. In fact, in the case of 15b-CHO (compounds 103,107,
109,111,113,117,119,138) the signal of the aldehydic proton can
be found in the range 9.94–9.91 d (brs), whereas if the aldehydic
group is a-orientated (compounds 101,102,104,105,108,110,
112,115,118,137), the proton signal is up-field shifted (9.68–9.33
d, d, J = 4.2–3.9 Hz). Also some eudesmanes show the presence of
a carboxy or carbomethoxy group at C-12, rather than the
c-lactone. Table 8 reports a complete list of all 13C NMR spectroscopic data quoted in the literature.
Guaianes comprise the most numerous class, containing 143
compounds (Table 9). They have all a 1,5-cis junction and, with
the exception of compounds 280–283, isolated from S. latifolia,
they are all trans-6,12 lactones. The presence of a C-8 oxygenated
function (a-alcohol or ester, never ketone) is also a common feature. There are, however, a few exceptions: 216 and 283 carry an
oxygenated function in C-1, while a few compounds carry this
function on C-9 (151, 153, 155, 156, 271). Also the occurrence of
a C-10/C-14 double bond is a common functionality, and only
152, 154, 262, 272, 273, and 280–282 have a different structural
moiety. Guaianes listed in Table 9 were grouped on the basis of
the C-4/C-15 functionality: double bound (142–205), epoxyde
(206–216), chlorohydrine (217–235), diol (236–261), methyl
Please cite this article in press as: Bruno, M., et al. Sesquiterpenoids in subtribe Centaureinae (Cass.) Dumort (tribe Cardueae, Asteraceae): Distribution, 13C
NMR spectral data and biological properties. Phytochemistry (2013), http://dx.doi.org/10.1016/j.phytochem.2013.07.002
6
M. Bruno et al. / Phytochemistry xxx (2013) xxx–xxx
Table 3
Germacranes isolated from taxa of the Subtribe Centaureinae.
No Structure
Name
Taxa
Ref.
1
costunolide
Centaurea acaulis
Bentamane et al. (2005)
Centaurea kurdica
Centaurea kurdica
Appendino and Özen (1993)
Appendino and Özen (1993)
3a,15-Dihydroxy-costunolide
Centaurea lusitanica
Nowak et al. (1989a), Nowak (1992)
Salonitenolide
Aegialophila pumila
Centaurea achaia
Centaurea affinis
Centaurea alba
Centaurea alba ssp. caliacrae
Centaurea alba ssp. deusta
Centaurea aspera
Centaurea aspera ssp.
scorpiurifolia
Centaurea aspera ssp. stenophylla
Centaurea bombycina
Centaurea calcitrapa
Centaurea crithmifolia
El-Marsy et al. (1984)
Skaltsa et al. (2000a)
Janaćković et al. (2004)
Fernandez et al. (1995)
Geppert et al. (1983)
Geppert et al. (1983)
Barrero et al. (1995)
Barrero et al. (1995)
O
O
2
8-Desoxy-salonitenolide;
15-hydroxycostunolide
OH
O
HO
O
3
HO
O
HO
O
4
HO
O
O
Centaurea
Centaurea
Centaurea
Centaurea
Centaurea
Centaurea
Centaurea
Centaurea
Centaurea
Centaurea
Centaurea
Centaurea
crocodylium
derventana
eriophora
friderici
grisebachii
iberica
malacitana
maroccana
melitensis
orphanidea
paniculata
paui
Centaurea pontica
Centaurea pseudomaculosa
Centaurea salonitana
Centaurea stoebe
Centaurea weldeniana
Cheriolophus intybaceus
Cnicus benedictus
5
Stenophyllolide
OH
HO
O
O
15-Hydroxy-8a-isobutyryloxycostunolide; 40 -desoxyarctiopicrin
6
O
Barrero et al. (1995), Marco et al. (2005)
Barrero et al. (2000)
Geppert et al. (1983), Jakupovic et al. (1986)
Geppert et al. (1983), Gousiadou and Skaltsa
(2003)
Horoszkiewicz-Hassan and Nowak (2001)
Tešević et al. (1998a)
Geppert et al. (1983)
Geppert et al. (1983)
Djeddi et al. (2008a)
Sham’yanov et al. (1998)
Barrero et al. (1988), Barrero et al., 1995
Barrero et al. (2000)
Barrero et al. (1989)
Gousiadou and Skaltsa (2003)
Geppert et al. (1983)
Cardona et al. (1997), Gousiadou and Skaltsa
(2003)
Geppert et al. (1983)
Turdybekov et al. (1989), Adekenov (1995)
Suchy et al. (1967), Rybalko et al. (1975),
Gonzalez et al. (1977a), Daniewski et al.
(1992), Nowak et al. (1996)
Huneck et al. (1986a)
Geppert et al. (1983)
Marco et al. (1994)
Vanhaelen-Fastre and Vanhaelen (1974),
Vanhaelen-Fastre and Vanhaelen (1976),
Vanhaelen and Vanhaelen-Fastre (1975),
Tsankova et al. (1994)
Marco et al. (2005)
Barrero et al. (1995)
Centaurea aspera
Centaurea aspera ssp.
scorpiurifolia
Centaurea aspera ssp. stenophylla Sanchez Paradera et al. (1968), Gonzalez
et al. (1977a), Picher et al. (1984a), Amigo
et al. (1984), Barrero et al. (1995), Marco
et al. (2005)
Centaurea aspera ssp. subinermis Cardona et al. (1991)
Centaurea lusitanica
Nowak et al. (1996)
Centaurea malacitana
Barrero et al. (1988), Barrero et al. (1995),
Barrero et al. (1997a)
Cheiroluphus intybaceus
Marco et al. (1994)
Cheiroluphus mauritanicus
Marco et al. (1994)
O
HO
O
O
Please cite this article in press as: Bruno, M., et al. Sesquiterpenoids in subtribe Centaureinae (Cass.) Dumort (tribe Cardueae, Asteraceae): Distribution, 13C
NMR spectral data and biological properties. Phytochemistry (2013), http://dx.doi.org/10.1016/j.phytochem.2013.07.002
7
M. Bruno et al. / Phytochemistry xxx (2013) xxx–xxx
Table 3 (continued)
No Structure
Name
Taxa
Ref.
7
8a-(20 -methyl-20 -propenoyl)salonitenolide; 15-hydroxy-8a-(amethylacryloyl)-costunolide
Centaurea achaia
Cheiroluphus intybaceus
Cheirolophus hortigenus
Skaltsa et al. (2000a)
Marco et al. (1994)
Marco et al. (1994)
Onopordopicrin
Centaurea
Centaurea
Centaurea
Centaurea
Centaurea
Centaurea
Centaurea
Centaurea
Centaurea
Centaurea
Centaurea
Centaurea
Cheirolophus x hortigenus
Cheiroluphus intybaceus
Skaltsa et al. (2000a)
Marco et al. (2005)
Marco et al. (2005)
Sarg et al. (1989)
Barrero et al. (2000)
Barrero et al. (1989)
Trendafilova et al. (2007)
Bruno et al. (1996)
Youssef (1998)
Lonergan et al. (1992)
Gonzalez et al. (1984), Nowak et al. (1986a)
Fortuna et al. (2001), Cabral et al. (2008),
Bach et al. (2011)
Marco et al. (1994)
Marco et al. (1994)
salonitenolide-8-(40 hydroxyisobutyrate);
arctiopicrin
Centaurea eryngioides
Centaurea gigantea
Centaurea melitensis
Sarg et al. (1989)
Shoeb et al. (2007a)
Barrero et al. (1989)
amarin
Centaurea amara
Centaurea malacitana
Centaurea nicaensis
Gonzalez et al. (1980a)
Barrero et al. (1988)
Bruno et al. (1996)
8a-Angeloyl-salonitenolide
Centaurea aspera ssp. stenophylla Marco et al. (2005)
Arbutifolin
Centaurea arbutifolia
Gonzalez et al. (1981)
8a-(40 -hydroxy-30 -methylbutanoyl)salonitenolide
Centaurea achaia
Centaurea gigantea
Skaltsa et al. (2000a)
Shoeb et al. (2007a)
8a-(40 -hydroxy-20 -methyl-20 butenoyl)-salonitenolide
Centaurea achaia
Skaltsa et al. (2000a)
OH
8a-(50 -hydroxytigloyl)-salonitenolide
Centaurea achaia
Centaurea glomerata
Cheiroluphus intybaceus
Skaltsa et al. (2000a)
El-Marsy et al. (1985)
Marco et al. (1994)
OH
8a-(50 -hydroxyangeloyl)salonitenolide
Centaurea aspera ssp. stenophylla Marco et al. (2005)
Centaurea moesiaca
Trendafilova et al. (2007)
Centaurea phrygia
Tsankova and Ognyanov (1985)
Cnicus benedictus
Tsankova et al. (1994)
O
O
HO
O
O
8
O
OH
O
HO
O
O
9
O
OH
O
HO
O
O
10
OAc
O
O
HO
achaia
aspera
aspera ssp. stenophylla
eryngioides
incana
melitensis
moesiaca
nicaensis
scoparia
sonchifolia
tagananensis
tweediei
O
O
11
O
O
HO
O
O
12
O
O
HO
O
O
13
O
OH
O
HO
O
O
14
O
OH
O
HO
O
O
15
O
O
HO
O
O
16
O
O
HO
O
O
(continued on next page)
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NMR spectral data and biological properties. Phytochemistry (2013), http://dx.doi.org/10.1016/j.phytochem.2013.07.002
8
M. Bruno et al. / Phytochemistry xxx (2013) xxx–xxx
Table 3 (continued)
No Structure
Name
Taxa
Ref.
17
8a-(40 -hydroxyangeloyl)salonitenolide
Centaurea glomerata
El-Marsy et al. (1985)
8a-(40 -acetoxyangeloyl)salonitenolide
Centaurea aspera ssp. stenophylla Marco et al. (2005)
Centaurea malacitana
Barrero et al. (1997a)
Cnicin
El-Marsy et al. (1984)
Mezache et al. (2010)
Bruno et al. (2001)
Janać ković et al. (2004), Tešević et al. (2007)
Gonzalez et al. (1977a), Nowak et al.
(1986a)
Centaurea aggregata
Nowak et al. (1984), Gousiadou and Skaltsa
(2003)
Centaurea alba
Gonzalez et al. (1977a), Fernandez et al.
(1995)
Centaurea alexandrina
Ismail et al. (1986)
Centaurea aplopea
Nowak et al. (1984), Gousiadou and Skaltsa
(2003)
Centaurea aplopea ssp. lunensis
Nowak et al. (1984), Gousiadou and Skaltsa
(2003)
Centaurea araneosa
Farrag et al. (1993)
Centaurea arenaria
Nowak et al. (1984), Gousiadou and Skaltsa
(2003), Tešević et al. (2007), Csapi et al.
(2010)
Centaurea arenaria ssp. majorowii Nowak et al. (1984), Gousiadou and Skaltsa
(2003)
Centaurea arenaria ssp. odesana
Nowak et al. (1984), Gousiadou and Skaltsa
(2003)
Centaurea aspera
Geppert et al. (1983), Barrero et al. (1995)
Centaurea aspera ssp.
Barrero et al. (1995)
scorpiurifolia
Centaurea aspera ssp. stenophylla Barrero et al. (1995), Marco et al. (2005)
Centaurea attica
Skaltsa et al. (1999), Gousiadou and Skaltsa
(2003)
Centaurea attica ssp. drakiensis
Nowak et al. (1984), Gousiadou and Skaltsa
(2003)
Centaurea attica ssp. ossaea
Nowak et al. (1984), Gousiadou and Skaltsa
(2003)
Centaurea bombycina
Barrero et al. (2000)
Centaurea bruguierana
Rustaiyan et al. (1982), Harraz et al. (1994)
Centaurea calcitrapa
Drozdz (1967), Rybalko et al. (1975),
Gonzalez et al. (1977a), Gonzalez et al.,
1978a, Karawya et al. (1975), Geppert et al.
(1983), Jakupovic et al. (1986), Marco et al.
(1992)
Centaurea calolepis
Baykan Erel et al. (2011)
Centaurea calvescens
Nowak et al. (1984), Gousiadou and Skaltsa
(2003)
Centaurea castellana
Gonzalez et al. (1977a)
Centaurea cineraria
Nowak et al. (1984), Gousiadou and Skaltsa
(2003)
Centaurea cinerar. ssp.
Bruno et al. (1998)
busambarensis
Centaurea cineraria ssp. umbrosa Bruno and Herz (1988);Gousiadou and
Skaltsa (2003)
Centaurea cineraria var. circae
Nowak et al. (1984), Gousiadou and Skaltsa
(2003)
Centaurea crocodylium
Horoszkiewicz-Hassan and Nowak (2001)
Centaurea cuneifolia
Salan and Öksük (1999), Gousiadou and
Skaltsa (2003), Tešević et al. (2007)
Centaurea cuneifolia ssp. pallida
Nowak et al. (1984), Gousiadou and Skaltsa
(2003)
Centaurea derventana
Tešević et al. (1998a)
Centaurea deusta
Karioti et al. (2002)
Centaurea diffusa
Drozdz (1966), Rybalko et al. (1975),
Gonzalez et al. (1977a), Milkova et al.
(1993), Fortuna et al. (2002), Gousiadou and
Skaltsa (2003), Cabral et al. (2008), Bach
et al. (2011)
O
O
HO
OH
O
O
18
O
O
HO
OAc
O
O
19
O
OH
O
HO
O
O
OH
Aegialophila pumila
Amberboa lippii
Centaurea aegialophila
Centaurea affinis
Centaurea africana
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NMR spectral data and biological properties. Phytochemistry (2013), http://dx.doi.org/10.1016/j.phytochem.2013.07.002
9
M. Bruno et al. / Phytochemistry xxx (2013) xxx–xxx
Table 3 (continued)
No Structure
Name
Taxa
Ref.
C. diffusa var. brevispina = C.
bovina
Centaurea eriophora
Centaurea eryngioides
Centaurea exarata
Nowak et al. (1984), Gousiadou and Skaltsa
(2003)
Geppert et al. (1983)
Sarg et al. (1989)
Nowak et al. (1984), Nowak et al. (1986a),
Gousiadou and Skaltsa (2003)
Tešević et al. (2007)
Barrero et al. (2000)
Nowak et al. (1984), Gousiadou and Skaltsa
(2003), Djeddi et al. (2008a)
Nowak et al. (1984), Gousiadou and Skaltsa
(2003)
Drozdz (1967), Rybalko et al. (1975),
Gonzalez et al. (1977a), Sham’yanov et al.
(1998)
Nowak et al. (1984), Gousiadou and Skaltsa
(2003)
Nowak et al. (1984), Gousiadou and Skaltsa
(2003)
Geppert et al. (1983), Nowak (1992), Nowak
et al. (1996)
Rybalko et al. (1975), Gonzalez et al.
(1977a), Kelsey and Locken (1987), Landau
et al. (1994), Gousiadou and Skaltsa (2003),
Meepagala et al. (2006)
Barrero et al. (1988), Barrero et al. (1995,
1997a)
Nowak et al. (1984), Gousiadou and Skaltsa
(2003)
Maymò et al. (1999)
Barrero et al. (2000), Bentamene et al.
(2007)
Drozdz (1968), Gonzalez et al. (1977a)
Trendafilova et al. (2007)
Barrero et al. (2000)
Bruno et al. (1995)
Bruno et al. (1996)
Nowak et al. (1984), Gousiadou and Skaltsa
(2003)
Drozdz (1967), Rybalko et al. (1975),
Gonzalez et al. (1977a)
Ali et al. (1987)
Nowak et al. (1984), Gousiadou and Skaltsa
(2003)
Bruno et al. (2002)
Centaurea glaberima (Tricholepis)
Centaurea granatensis
Centaurea grisebachi
Centaurea grisebachi ssp. confusa
Centaurea iberica
Centaurea kartschiana
Centaurea leucophaea
Centaurea lusitanica
Centaurea maculosa
Centaurea malacitana
Centaurea mantoudii
Centaurea mariolensis
Centaurea maroccana
Centaurea
Centaurea
Centaurea
Centaurea
Centaurea
Centaurea
micranthos
moesiaca
monticola
napifolia
nicaensis
orphanidea
Centaurea ovina
Centaurea pallescens
Centaurea pallidior
Centaurea paniculata ssp.
castellana
Centaurea paui
Centaurea
Centaurea
Centaurea
Centaurea
Centaurea
Centaurea
Centaurea
Centaurea
Centaurea
Centaurea
Centaurea
Centaurea
Centaurea
Centaurea
Centaurea
Cardona et al. (1997), Gousiadou and Skaltsa
(2003)
pelia
Nowak et al. (1984), Gousiadou and Skaltsa
(2003)
pseudomaculosa
Adekenov et al. (1979, 1986a), Adekenov
(1995)
raphanina ssp. mixta
Panagouleas et al. (2003)
rhenana ssp. savranica Nowak et al. (1984), Gousiadou and Skaltsa
(2003)
rocheliana
Geppert et al. (1983)
rothmalerana
Santos et al. (1995)
sphaerocephala
Bruno et al. (1994)
spinosa
Nowak et al. (1984), Gousiadou and Skaltsa
(2003), Saroglou et al. (2005)
splendens
Tešević et al. (2007)
squarrosa
Tarasov et al. (1973), Gonzalez et al.
(1977a), Isamukhamedova et al. (1977)
stoebe
Suchy and Herout (1962), Rybalko et al.
(1975), Gonzalez et al. (1977a), Huneck
et al. (1986a), Tešević et al. (2007)
sulphurea
Geppert et al. (1983), Gonzalez et al. (1984),
Barrero et al. (2000), Lakhal et al. (2010)
thessala ssp. drakiensis Skaltsa et al. (1999), Georgiadou et al.
(2000), Gousiadou and Skaltsa (2003)
transiens
Nowak et al. (1984), Gousiadou and Skaltsa
(2003)
tymphaea
Nowak et al. (1984), Gousiadou and Skaltsa
(2003)
(continued on next page)
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NMR spectral data and biological properties. Phytochemistry (2013), http://dx.doi.org/10.1016/j.phytochem.2013.07.002
10
M. Bruno et al. / Phytochemistry xxx (2013) xxx–xxx
Table 3 (continued)
No Structure
Name
Taxa
Ref.
Centaurea tymphaea ssp.
brevispina
Centaurea vallesiaca
Nowak et al. (1984), Gousiadou and Skaltsa
(2003)
Geppert et al. (1983), Landau et al. (1994),
Gousiadou and Skaltsa (2003)
Nowak et al. (1984), Koukoulitsa et al.
(2002), Gousiadou and Skaltsa (2003)
Korte and Beckmann (1958), Suchy et al.
(1959a), Suchy et al. (1959b), Suchy et al.
(1960), Vanhaelen-Fastre (1968),
Vanhaelen-Fastre (1972), Samek et al.
(1969), Rybalko et al. (1975), VanhaelenFastre and Vanhaelen (1976), Tsankova et al.
(1994), Kataria (1995)
Karioti et al. (2002)
Centaurea zuccariniana
Cnicus benedictus
Cnicin 30 -O-acetyl
20
O
O
HO
OAc
O
O
Cnicin 40 -O-acetyl
21
O
OAc
O
HO
Centaurea deusta
OH
OH
O
O
22
8a-(40 ,50 -dihydroxytigloyloxy)salonitenolide
OH
O
Centaurea moesiaca
Trendafilova et al., 2007
Centaurea alba
Fernandez et al. (1995)
Centaurea aspera
Barrero et al. (1995)
Centaurea aspera ssp.
Barrero et al. (1995)
scorpiurifolia
Centaurea aspera ssp. stenophylla Barrero et al. (1995), Marco et al. (2005)
Centaurea attica
Skaltsa et al. (1999), Gousiadou and Skaltsa
(2003)
Centaurea calcitrapa
Jakupovic et al. (1986), Marco et al. (1992)
Centaurea cineraria ssp. umbrosa Bruno and Herz (1988), Gousiadou and
Skaltsa (2003)
Centaurea derventana
Tešević et al. (1998a)
Centaurea deusta
Karioti et al. (2002)
Centaurea diffusa
Fortuna et al. (2002)
Centaurea malacitana
Barrero et al. (1988, 1995, 1997a)
Centaurea mariolensis
Maymò et al. (1999)
Centaurea maroccana
Barrero et al. (2000)
Centaurea moesiaca
Trendafilova et al. (2007)
Centaurea monticola
Barrero et al. (2000)
Centaurea napifolia
Bruno et al. (1995)
Centaurea orphanidea
Gousiadou and Skaltsa (2003)
Centaurea paniculata ssp.
Bruno et al. (2002)
castellana
Centaurea paui
Cardona et al. (1997), Gousiadou and Skaltsa
(2003)
Centaurea sphaerocephala
Bruno et al. (1994)
Centaurea spinosa
Saroglou et al. (2005)
Centaurea thessala ssp. drakiensis Skaltsa et al. (1999), Georgiadou et al.
(2000), Gousiadou and Skaltsa (2003)
Centaurea zuccariniana
Koukoulitsa et al. (2002)
Cnicus benedictus
Tsankova et al. (1994)
Centaurea achaia
Skaltsa et al. (2000a)
OH
O
HO
O
O
23
OH
O
OAc
8a-O-(40 -acetoxy-20 hydroxymethylbuten-20 -oyloxy)salonitenolide
Centaurea spinosa
Salonitenolide-8-O-(40 -acetoxy-50 hydroxy-angelate)
Centaurea
Centaurea
Centaurea
Centaurea
Centaurea
Centaurea
Centaurea
Centaurea
Centaurea
Saroglou et al. (2005)
O
HO
O
O
24
OH
O
O
HO
O
O
OAc
Fernandez et al. (1995)
Marco et al. (2005)
Marco et al. (2005)
Barrero et al. (2000)
Karioti et al. (2002)
Tešević et al. (1998a)
Djeddi et al. (2008a)
Trendafilova et al. (2007)
Cardona et al. (1997), Gousiadou and Skaltsa
(2003)
Centaurea stoebe
Huneck et al. (1986a)
Centaurea thessala ssp. drakiensis Skaltsa et al. (1999)
alba
aspera
aspera ssp. stenophylla
bombycina
deusta
derventana
grisebachi
moesiaca
paui
Please cite this article in press as: Bruno, M., et al. Sesquiterpenoids in subtribe Centaureinae (Cass.) Dumort (tribe Cardueae, Asteraceae): Distribution, 13C
NMR spectral data and biological properties. Phytochemistry (2013), http://dx.doi.org/10.1016/j.phytochem.2013.07.002
11
M. Bruno et al. / Phytochemistry xxx (2013) xxx–xxx
Table 3 (continued)
No Structure
Name
Taxa
Ref.
25
Centaurea moesiaca
Trendafilova et al. (2007)
OH
OH
1b,15-dihydroxy-8a-(3,4-dihydroxy2- methylenebutanoyloxy)4E,10(14),11(13)-germacratriene12,6a- olide
Centaurea moesiaca
Trendafilova et al. (2007)
OH
OH
1a,15-dihydroxy-8a-(3,4-dihydroxy2- methylenebutanoyloxy)4E,10(14),11(13)-germacratriene12,6a- olide
stizolin
Stizolophus balsamita
Mukhametzhanov et al. (1969a, 1971),
Rybalko et al. (1975), Gonzalez et al.
(1977a),Nowak (1992), Suleimenov et al.
(2005a)
9a-hydroxypartenolide
Zoegea baldshuanica
Buděšinský et al. (1984), Nowak (1992),
Nowak et al. (1996)
8a,9a-dihydroxypartenolide
Stizolophus balsamita
Mukhametzhanov et al. (1969a), Nowak
et al. (1996), Nowak (1992)
8,15-dihydroxy-1(10)-epoxygermacr-4-ene
Centaurea sphaerocephala
Bruno et al. (1994)
1(10)-en-4a,5b-epoxy-8a-(40 hydroxysenecioate)-germacrane
Centaurea coronopifolia
Öksüz and Ayyildiz (1986)
stizolicin
Centaurea coronopifolia
OH
O
O
O
HO
26
O
OH
O
O
O
HO
O
27
OH
O
O
O
28
OH
O
O
O
29
OH
OH
O
O
O
30
O
OH
O
HO
O
31
O
OH
O
O
O
O
32
OH
O
balsamin
Stizolophus balsamita
Mukhametzhanov et al. (1969b, 1970),
Rybalko et al. (1975), Öksüz and Ayyildiz
(1986)
Mukhametzhanov et al. (1969c), Rybalko
et al. (1975), Gonzalez et al. (1977a),
Naidenova et al. (1988)
Rybalko et al. (1975), Cassady et al. (1984),
Nowak (1992)
Rybalko et al. (1976), Nowak (1992)
9-epi-balsamin
Centaurea coronopifolia
Stizolophus balsamita
Öksüz and Ayyildiz (1986)
Suleimenov et al. (2005a)
8a-(40 -hydroxy-sencioyloxy)-9ahydroxy-parthenolide; 9-epi-40 hydroxybalsamin
Centaurea coronopifolia
Öksüz and Ayyildiz (1986)
Stizolophus balsamita
Nowak et al. (1989b, 1996), Nowak (1992),
Suleimenov et al. (2005a)
OH
Centaurea solstitialis
O
O
O
Stizolophus balsamita
O
33
OH
O
O
O
O
O
34
OH
O
O
O
O
O
35
OH
O
OH
O
O
O
O
(continued on next page)
Please cite this article in press as: Bruno, M., et al. Sesquiterpenoids in subtribe Centaureinae (Cass.) Dumort (tribe Cardueae, Asteraceae): Distribution, 13C
NMR spectral data and biological properties. Phytochemistry (2013), http://dx.doi.org/10.1016/j.phytochem.2013.07.002
12
M. Bruno et al. / Phytochemistry xxx (2013) xxx–xxx
Table 3 (continued)
No Structure
36
OH
Name
Taxa
11b,13-dihydrosalonitenolide
Centaurea
Centaurea
Centaurea
Centaurea
Centaurea
Centaurea
Centaurea
O
HO
O
37
8-oxo-15-hydroxygermacra1(10),E,4Z-dien-11bH-12,6a-olide
O
Ref.
achaia
alba
aspera
calcitrapa
maroccana
nicaensis
paui
Centaurea pullata
Centaurea aspera
Skaltsa et al. (2000a)
Fernandez et al. (1995)
Marco et al. (2005)
Marco et al. (1992)
Barrero et al. (2000)
Medjroubi et al. (2003a)
Cardona et al. (1997), Gousiadou and Skaltsa
(2003)
Djeddi et al. (2008b)
Marco et al. (2005)
O
HO
O
38
OH
11bH,13-dihydrostenophyllolide
Centaurea aspera
Marco et al. (2005)
Centaurea aspera ssp. stenophylla Marco et al. (2005), Picher et al. (1984b)
Centaurea aspera ssp. subinermis Cardona et al. (1991)
11bH,13-dihydroonopordopicrin
Centaurea glomerata
El-Marsy et al. (1985)
dihydroamirin
Centaurea amara
Centaurea nicaensis
Gonzalez et al. (1980a)
Bruno et al. (1996)
11,13-dihydroarbutifolin
Centaurea arbutifolia
Gonzalez et al. (1981)
8a-(40 -hydroxy-30 -methylbutanoyl)11b,13- dihydrosalonitenolide
Centaurea achaia
Skaltsa et al. (2000a)
8a-(40 -hydroxy-20 -methyl-20 butenoyl)-11b,13dihydrosalonitenolide
Centaurea glomerata
El-Marsy et al. (1985)
11b,13-dihydro-19-desoxycnicin
Centaurea pullata
Benayache et al. (1992), Djeddi et al. (2007)
11b,13-dihydrocnicin
Centaurea nicaensis
Centaurea pullata
Bruno et al. (1996), Medjroubi et al. (2003a)
Benayache et al. (1992), Djeddi et al. (2007)
8a-O-(40 -acetoxy-50 hydroxyangeloyl)-11b,13dihydrosalonitenolide
Centaurea pullata
Djeddi et al. (2007)
11,13-dihydrostizolin
Stizolophus balsamita
Suleimenov et al. (2005a)
O
HO
O
39
O
OH
O
O
HO
O
40
O
OAc
O
O
HO
O
41
O
O
O
HO
O
42
O
OH
O
O
HO
O
43
O
OH
O
O
HO
O
44
O
OH
O
O
HO
O
45
O
OH
O
OH
O
HO
O
46
OH
O
O
OAc
O
HO
O
47
OH
O
O
O
Please cite this article in press as: Bruno, M., et al. Sesquiterpenoids in subtribe Centaureinae (Cass.) Dumort (tribe Cardueae, Asteraceae): Distribution, 13C
NMR spectral data and biological properties. Phytochemistry (2013), http://dx.doi.org/10.1016/j.phytochem.2013.07.002
13
M. Bruno et al. / Phytochemistry xxx (2013) xxx–xxx
Table 3 (continued)
No Structure
Name
Taxa
Ref.
48
11a,13-dihydro-8desoxysalonitenolide
Centaurea kurdica
Appendino and Ö zen (1993)
11a,13-dihydrosalonitenolide
Centaurea calcitrapa
Marco et al. (1992)
Cebellin M
Centaurea bella
Nowak (1992, 1993a,b), Nowak et al. (1996)
germacra-1(10),4-dien-6b-ol
Phonus arborescens
Barrero et al. (1997b)
shiromool
Phonus arborescens
Barrero et al. (1997b)
artemisiifolin
Centaurea castellana
Gonzalez et al. (1984), Gousiadou and
Skaltsa (2003)
Nowak et al. (1996)
Gonzalez et al. (1973a, 1977a)
Gonzalez et al. (1984)
Nowak et al. (1996)
Vanhaelen-Fastre and Vanhaelen (1976)
Nowak et al. (1996)
Gonzalez et al. (1973a, 1977a)
Gonzalez et al. (1984)
Nowak et al. (1996)
O
HO
O
49
OH
O
HO
O
50
OH
O
AcO
O
51
OH
52
O
OH
53
O
O
OH
HO
54
15-Acetylartemisiifolin
O
O
OH
AcO
55
Scabiolide
O
Centaurea polyacantha
Centaurea seridis
Centaurea sonchifolia
Centaurea sphaerocephala
Cnicus benedictus
Centaurea polyacantha
Centaurea seridis
Centaurea sonchifolia
Centaurea sphaerocephala
Centaurea solstitialis
Suchy et al. (1962a,b, 1965a, 1968), Rybalko
et al. (1975), Gonzalez et al., 1977a
Mukhametzhanov et al. (1969c)
isospiciformin
Stizolophus balsamita
Nowak et al. (1989b, 1996), Nowak (1992)
Salonitolide
Centaurea salonitana
Suchy et al. (1965b), Rybalko et al. (1975),
Gonzalez et al. (1977a), Daniewski et al.
(1992)
Gonzalez et al. (1973a, 1977a)
Centaurea scabiosa
O
OH
AcO
O
OH
O
56
O
O
O
OH
57
O
O
Centaurea seridis
OH
HO
58
OH
O
O
Onopordopicrin-valine dimeric
adduct
Centaurea aspera ssp. stenophylla Marco et al. (1991), Marco et al., 2005
15-acetoxy-8a-hydroxy-7aH,6bHgermacra-4E, 1(10),11(13)-trien12,6-olide
Centaurea paui
Cardona et al. (1997)
15-acetoxy-1b,8a-dihydroxy7aH,6bH- germacra4E,10(14),11(13)-trien-12,6-olide
Centaurea paui
Cardona et al. (1997), Gousiadou and Skaltsa
(2003)
O
O
N
O
HO
O
O
HO
59
OH
O
O
O
OH
OH
AcO
OH
O
AcO
60
O
N
O
O
(continued on next page)
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NMR spectral data and biological properties. Phytochemistry (2013), http://dx.doi.org/10.1016/j.phytochem.2013.07.002
14
M. Bruno et al. / Phytochemistry xxx (2013) xxx–xxx
Table 3 (continued)
No Structure
Name
Taxa
Ref.
61
15-acetoxy-1b-hydroperoxy-8ahydroxy-7aH,6bH-germacra4E,10(14),11(13)-trien-12,6-olide
Centaurea paui
Cardona et al. (1997), Gousiadou and Skaltsa
(2003)
15-acetoxy-1b,10a-epoxy-8ahydroxy- 7aH,6bH-germacra4E,11(13)-dien-12,6-olide
Centaurea paui
Cardona et al. (1997), Gousiadou and Skaltsa
(2003)
8-(40 -hydroxy-methacroyloxy)-15oxohelianga-1(10)-4,11(13)-trien6,12-olide
Centaurea tweediei
Fortuna et al. (2001)
OOH
OH
O
AcO
O
62
O
OH
O
AcO
O
63
OH
O
O
CHO
O
O
15-acetoxy-8a-O-(3,4-dihydroxy-2Centaurea paui
methylene-butanoyloxy)- 7aH,6bHgermacra-4E,1(10),11(13)-trien-12,6olide
Centaurea sulphurea
Cardona et al. (1994)
15-acetoxy-8a-O-(3,hydroxy4acetoxy-2-methylenebutanoyloxy)- 7aH,6bH-germacra4E,1(10),11(13)-trien-12,6-olide
Centaurea paui
Cardona et al. (1994)
Sulphurein
Centaurea sulphurea
Lakhal et al. (2010)
Cardona et al. (1997), Gousiadou and Skaltsa
(2003)
OH
15-acetoxy-8a-O-(3,4-dihydroxy-2methylene-butanoyloxy)- 1bhydroxy-7aH,6bH-germacra4E,10(14), 11(13)-trien-12,6-olide
Centaurea paui
OH
Centaurea paui
Cardona et al. (1997), Gousiadou and Skaltsa
(2003)
OH
OH
15-acetoxy-8a-O-(3,4-dihydroxy-2methylene-butanoyloxy)- 1bhydroperoxy-7aH,6bH-germacra4E,10(14), 11(13)-trien-12,6-olide
64
O
OH
O
OH
O
AcO
Lakhal et al. (2010)
O
65
O
OAc
O
OH
O
AcO
O
66
O
OH
O
CHO
OH
O
O
67
OH
O
O
O
AcO
68
O
OOH
O
O
AcO
O
O
(262–283) and C15-nor (284). Table 10 reports a complete list of all
13
C NMR spectroscopic data quoted in the literature. In contrast to
the other classes of sesquiterpenes, the guaianes of Centaurineae
have a large variety of side chain esters linked at C-8 and many
of them have a stereogenic center at C-20 . A useful tool has been
identify in order to determinate the absolute stereochemistry of
the C-20 carbon of the side chain. In fact as reported in Table 11
the 1H NMR values of the epimeric side chains are practically identical whereas the diagnostic signal is H13b. In the case of a C-20 R
stereochemistry it resonates in the range (CDCl3) d 5.56–5.64,
instead for a C-20 S stereochemistry the range is d 5.71–6.07
(Table 11).
2.5. Others
Four sesquiterpenes with different skeletons are listed in
Table 12 and the 13C NMR spectroscopic data of carabrone (287)
is inserted in Table 10.
3. Chemotaxonomic remarks
The analysis of sesquiterpene skeletons (Table 13) occurring in
the 210 taxa belonging to the subtribe Centaureinae, reveals the
presence of two main classes: 75 taxa contain exclusively guaianetype sesquiterpenes whereas 68 taxa contain exclusively germacrane-type sesquiterpenes. Only 12 skeleton combinations among the
15 possible occur in this subtribe. No taxa contains at the same time
all the four skeletons neither guaines, eudesmanes and elemanes,
nor elemanes alone. Only five species do not contain either guianes
or germacranes (Centaurea cadmea, Centaurea granata, Centaurea
hierapolitana, Centaurea phyllocephala, Centaurea pamphilica).
Furthermore,Centaurea conifera, Centaurea incana, Centaurea
salonitana, Centaurea scabiosa and C. solstitialis have been shown
to have germacranes, guaianes or eudesmane depending on the
collection place.
It is noteworthy that only one species (Centaurea chilensis) contains both guaines and elemanes but they were found in two separate investigations.
Please cite this article in press as: Bruno, M., et al. Sesquiterpenoids in subtribe Centaureinae (Cass.) Dumort (tribe Cardueae, Asteraceae): Distribution, 13C
NMR spectral data and biological properties. Phytochemistry (2013), http://dx.doi.org/10.1016/j.phytochem.2013.07.002
C
1a1
2a2
4a3
5n:r:
4
6a5
7a5
8a6
8b3
8c7
9c7
9d8
10n:r:
4
11a3
13a2
13d8
14a9
15a5
16a3
18a3
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
10
20
30
40
50
100
200
127.1
26.3
39.5
140.1
127.3
81.9
50.4
28.2
41.0
136.9
141.5
170.5
119.6
16.1
17.3
126.5
28.6
35.4
143.3
128.8
80.1
50.5
27.7
40.8
137.7⁄
139.5⁄
170.2
120.0
15.9
61.2
128.7
26.3
35.0
143.6
128.5
76.5
54.7
70.9
52.5
134.0
136.3
171.1
127.0
16.9
60.9
127.4⁄
25.3
34.5
143.3
126.0⁄
77.8
46.6
35.7
79.5
140.0
n.r.
169.5
119.0
10.4
58.7
129.5
26.4
34.7
143.8
128.8
77.2
52.9
72.3
48.9
132.6
135.4
169.7
125.4
16.7
61.5
176.0
34.1
19.3
18.5
129.6
26.4
34.7
143.8
128.7
77.1
53.1
72.9
48.8
132.7
135.5
169.8
125.3
16.8
61.6
166.1
136.2
126.4
18.4
129.7
26.0
34.5
144.5
127.9
77.3
52.8
72.8
48.8
132.1g
135.2g
170.5h
125.6
16.6
60.5
165.0h
139.6g
125.7
60.9
129.8
26.3
34.7
144.2
128.4
76.6
53.0
73.1
48.7
132.4
135.4
169.9
125.5
16.8
61.3
165.1
139.4
126.3
62.1
129.9
26.4
34.5
144.7
128.6
76.9
53.0
73.2
48.7
132.6
136.9
169.8
124.3
16.5
60.4
165.2
141.5
123.7
60.8
130.1
26.8
34.9
145.0
128.6
77.1
52.9
73.1
49.2
133.3
137.0
170.3
128.8
16.8
60.6
174.8
43.4
64.3
14.0
129.5
25.7
34.0
144.9
128.5
77.3
52.4
72.8
48.4
132.3
135.9
171.0
124.8
15.7
59.6
174.7
42.7
63.6
12.8
130.4
26.8
34.9
145.1
129.0
77.4
53.5
74.0
49.1
133.0
137.4
170.1
123.9
16.9
60.9
165.5
141.6
127.2
67.9
129.5
26.3
34.7
143.8
128.8
76.7
53.0
72.2
49.0
132.7
135.6
169.8
125.1
16.9
61.5
166.8
127.3
139.5
15.9
20.5
129.5
26.3
34.7
143.8
128.7
76.6
52.7
72.5
49.0
132.6
135.3
169.7
125.8
16.7
61.4
172.1
38.4
32.7
61.7
16.7
129.8
26.4
33.8l
144.9
128.3
76.9
52.0
72.7
48.7
132.7
136.9
170.2
124.7
17.1
59.7
174.1
38.3
33.4
65.9
17.0
129.6
26.3
29.7
143.7
128.6
76.4
53.0
72.9
48.7
133.2
135.5⁄
169.7
125.2
16.7
61.5
166.1
135.0⁄
141.3
59.8
12.8
129.7
26.4
34.8
143.7
128.6
76.5
53.1
73.0
48.8
132.6
135.5
169.7
125.3
16.8
61.6
166.2
132.1
141.5
14.4
56.9
129.8
26.3
34.7
143.9
128.6
76.6
53.0
72.8
48.9
132.4
135.5
169.8
125.3
16.8
61.5
166.1
131.6
141.7
15.9
64.9
129.8
26.3
34.6
143.9
128.6
76.7
52.9
73.0
48.8
132.4
135.6
169.7
125.0
16.8
61.5
165.7
128.2
140.1
62.8
19.7
170.8
20.9
C
19b3
19c10
19e11
21a3
22e12
24a3
25b13
26b13
27a14
28a14
35a15
36a16
36b17
36a;n
17
37a3
38a18
39a2
44a19
45a19
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
10
20
30
40
50
100
200
129.8
26.1
34.6
144.6
128.0
77.1
53.0
73.1
48.6
132.1
135.3
170.5
125.5
16.7
60.7
165.1
139.7
70.8
65.8
127.1
130.8
26.8
35.5
145.6
129.6
78.7
54.1
74.6
47.0
133.1
137.3
172.0
125.2
17.0
60.9
166.6
142.4
71.8
66.7
127.2
130.9
26.9
35.2
145.5
129.7
78.7
54.1
74.5
49.0
133.2
137.4
172.1
125.3
17.0
60.7
166.6
142.3
71.9
66.7
127.0
129.9
26.3
34.7
144.1
128.4
76.4
53.0
73.3
48.6
132.3
135.4
169.8
125.3
16.8
61.5
164.6
138.8
69.5
67.3
127.8
171.3
20.8
131.1
27.4
35.4
145.7
130.1
78.9
54.2
74.8
48.9
133.0
137.6
172.5g
125.9
17.4
61.1
167.5g
133.7
147.2
59.7
57.0
129.8
26.1
34.6
144.3
128.2
76.9
52.7
73.3
48.7
132.1
135.4
170.2
125.3
16.8
60.8
164.8
131.7
140.3
62.8
62.3
171.1
20.8
77.2
34.2
28.0
147.6g
121.8
75.2
50.9
73.3
29.5
136.8
137.1
170.2h
121.8
118.1
61.0
164.4h
139.7g
70.5
65.4
126.9
76.2
33.9
28.3
147.4g
121.7
75.9
50.3
73.8
30.1
136.6
137.0
170.8h
121.6
117.9
61.1
164.2h
140.1g
72.4
66.0
127.1
128.0
24.7
35.7
61.5
66.4
78.3
52.2
71.3
52.0
130.0
134.0
169.8
128.5
18.1
17.4
121.9
23.5
36.3
61.3
66.6
82.4
37.6
37.6
71.4
137.5
139.8
169.4
121.1
16.4
17.3
126.6g
23.5h
35.9h
60.7
66.8i
80.6i
34.0i
75.5i
75.5i
133.7
133.5j
169.6
125.5
13.9k
17.1k
166.1
111.8g
160.5j
66.6
15.5k
128.2
25.9
34.7
142.6
129.3
76.6
59.9
71.4
52.2
133.9
40.6
180.3
17.3
16.8
60.4
128.6
26.1
34.9
142.7
129.5
76.4
60.1
72.0
52.9
133.9
40.8
179.9
17.6
17.1
61.1
129.4
26.1
35.0
138.0
131.6
76.1
58.2
72.9
49.1
132.9
40.3
177.7
17.0
16.8
61.6
170.7
21.2
169.8
21.0
132.3
24.8
33.4
145.1
128.3
75.3
64.4
203.6
57.4
126.5
40.5
177.1
13.6
16.0
60.1
127.2⁄
25.4
34.6
141.8
127.7⁄
78.5#
51.0
35.9
78.8#
139.1
41.2
177.6
12.5
10.0
59.7
129.4⁄
26.1
34.7
142.8
129.0⁄
76.1
58.3
73.8
49.0
132.6
40.2
178.0
17.0
16.6
61.5
165.3
139.3
126.3
62.4
129.3
25.7
34.3
143.3g
128.3
76.3
58.0h
73.3
48.8
132.4g
39.9h
178.9
16.6
16.3
60.3
166.6
137.0g
34.9
60.6
127.4
129.2
25.5
34.1
143.1g
128.0
76.3
57.8h
73.1
48.6
132.1g
39.8h
178.9i
16.0
16.4
59.8j
164.8i
139.7g
70.3
65.3j
126.2
C
46a20
48a21
49a;n
17
51a;o
22
53a23
53c23
f;m
5824
59a25
60a26
62a26
64a25
65a25
66a27
67a26
68a26
1
2
3
4
5
6
129.3
26.0
34.5
142.9
128.7
75.9
125.6
25.2
40.9
141.8
129.3
79.2
129.3
26.5
35.3
137.1
130.8
75.0
121.3
25.2
35.7
133.0
131.4
68.6
128.9
24.9
36.1
140.4
128.9
69.2
131.3
26.1
32.1
141.6
129.7
71.4
129.8
26.5
35.0
144.6
129.2⁄
77.4
127.6
24.5
25.8
134.8
125.7
76.7
72.0
31.0
24.5
134.7
125.7
75.0
61.5
26.3
24.7
134.0
125.3
75.2
128.5
24.6
27.0
134.2
125.4
76.5
128.7
24.7
27.1
134.3
125.3
76.4
127.8
24.1
22.3
142.0
146.7
75.6
72.3
31.1
24.5
134.2
125.3
74.7
85.7
26.2
24.4
134.4
125.6
74.5
170.9
20.7
⁄
15
(continued on next page)
M. Bruno et al. / Phytochemistry xxx (2013) xxx–xxx
Please cite this article in press as: Bruno, M., et al. Sesquiterpenoids in subtribe Centaureinae (Cass.) Dumort (tribe Cardueae, Asteraceae): Distribution, 13C
NMR spectral data and biological properties. Phytochemistry (2013), http://dx.doi.org/10.1016/j.phytochem.2013.07.002
Table 4
C NMR data of germacranes.
13
16
169.1
20.8
n.r.
20.9
170.5
20.9
177.6
69.5
32.1
20.1
19.0
n.r. = not reported. a In CDCl3. b In CDCl3/MeOD. c In acetone-d6. d In DMSO-d6. e In CD3OD. f In pyridine-d5. g,h,i,j,k Inverted with respect to the original paper. l Amended with respect to the original paper. m Spectrum not assigned in
the original paper. n As acetate. o P/b,a/N conformer. ⁄, ,# These values may be interchanged.
1
Hibasami et al. (2003); 2Lazari et al. (1998); 3Marco et al. (2005); 4Barrero et al. (1988); 5Marco et al. (1994); 6Lonergan et al. (1992); 7Barrero et al. (1989); 8Shoeb et al. (2007a); 9Garcia et al. (1996); 10Santos et al. (1995); 11Csapi
et al. (2010); 12Skaltsa et al. (2000a); 13Trendafilova et al. (2007); 14Bruno et al. (1991a); 15Suleimenov et al. (2005a); 16Medjroubi et al. (2003a); 17Marco et al. (1992); 18Cardona et al. (1991); 19Benayache et al. (1992); 20Djeddi
et al. (2007); 21Appendino and Özen (1993); 22Barrero et al. (1999); 23Jimeno et al. (2004); 24Marco et al. (1991); 25Cardona et al. (1994); 26Cardona et al. (1997); 27Lakhal et al. (2010).
50.0
74.4
41.1
139.0
138.2
169.0
127.2
120.4
66.2
164.8
138.3
71.2
65.7
127.0
170.7
20.9
50.2
74.2
40.2
143.5
138.1
168.9
127.2
116.3
66.1
164.7
139.1
71.3
65.7
127.0
170.5
20.8
49.1
69.1
45.5
131.6
132.8
169.2
129.9
15.0
194.0
164.8
139.3
70.1
65.0
126.1
50.5
69.5
46.3
131.1
136.7
169.1
127.4
16.8
66.9
164.4
138.5
70.2
67.4
127.1
170.5
20.8
171.3
20.9
50.5
70.1
46.1
131.1
136.7
169.5
127.5
16.7
66.8
164.8
139.4
70.9
65.7
126.6
170.5
20.8
52.6
67.4
49.0
56.3
137.2
170.4
128.4
16.7
66.6
52.3
72.5
43.0
144.3
137.5
n.r.
127.7
115.4
66.2
52.5
67.3
49.0
132.1
136.3
169.9
127.7
16.9
67.0
52.9
74.1
49.4
133.1
47.0
178.3
49.6
16.9
60.8#
165.9
142.5
124.1
61.2#
52.3
81.3
42.7
128.6
138.1
170.7
126.3
21.5
61.1
50.7
81.1
41.0
129.6
135.1
171.4
127.4
21.1
61.5
49.3
24.3
39.0
135.7
31.7
21.5
21.2
17.0
16.4
53.4
70.7
47.5
133.4
39.6
178.1
10.6
16.6
61.7
170.7
21.2
169.8
20.9
57.9
73.6
49.0
132.6
39.8
177.8
16.9
16.5
61.3
164.5
131.5
140.4
62.7
62.4
170.6
20.7
7
8
9
10
11
12
13
14
15
10
20
30
40
50
100
200
1000
2000
3000
49.5
26.6
35.3
137.2
40.9
179.7
10.8
15.9
60.7
46a20
C
Table 4 (continued)
48a21
49a;n
17
51a;o
22
53a23
53c23
58f;m
24
59a25
60a26
62a26
64a25
65a25
66a27
67a26
68a26
M. Bruno et al. / Phytochemistry xxx (2013) xxx–xxx
Starting from botanical considerations the distribution of sesquiterpenes within the groups of Centaureinae provides useful
information.
Almost all of the six genera (39 taxa) belonging to the first
group of Centaureinae, named ‘‘Basal genera’’ (Psephellus, Rhaponticoides, Cheirolophus, Plectocephalus, Stizolophus and Zoegea) contain guaianes with the exception of Stizolophus and Zoegea which
show the presence of germacranes only.
The representatives of Psephellus usually contain only guaianes.
All the analyses (incl. molecular approaches) confirm that Rhaponticoides (=Centaurea sect. Centaurea) and related taxa are a very isolated group of species. This group is always placed in a basal
position, far removed from the bulk of the genus (Garcia-Jacas
et al., 2006). A recent survey of Centaureinae and Plectocephalus
(Susanna et al., 2011), based on nuclear internal transcribed spacers (ITS) analyses, identified Stizolophus and Zoegea as sisters to the
rest of this group.
Four of the five species included in the second group of Centaureinae, Volutaria, contain only guaianes, the fifth species,Amberboa
lippii, in addition has the germacrane 19.
All the taxa of the third group, Rhaponticum, except Leuzea conifera and Raponticum uniflorum, possess guaianes. This group of
about 40 species ranged among the early branching taxa of Asteraceae, Centaureinae, according to the recent phylogenetic reconstructions based on molecular data (Hidalgo et al., 2006).
The fourth group (Serratula) contains only guaianes and
eudesmanes. The only studied species of the fifth group (Carthamus) Carthamus arborescens, contains germacranes and eudesmanes, but not guaianes, while the studied species of the sixth
group, Crocodylium, – germacranes and elemanes. The ITS phylogeny suggests that Aegialophila and Crocodylium form a strongly
supported clade, more connected to the Carthamus complex than
to the Acrocentron group (Garcia-Jacas et al., 2006).
With regard to the seventh group, Centaurea, we analyzed data
about the sesquiterpenoids of 153 taxa belonging to 19 sections:
Acrocentron, Calcitrapa, Acrolophus, Phalolepis, Jacea, Seridia, Microlophus, Tetramorphaea, Lepteranthus, Cheirolepis, Cyanus, Cynaroides,
Cheirolepis, Ptosimopappus, Melanoloma, Pseudophaeopappus, Solstitiaria, Chartolepis, Grossheimia.
Our research on sesquiterpenoids of the 63 taxa of sections
Acrolophus and Phalolepis shows that all representatives, except
Centaurea exarata and C. incana, do not contain guaianes. The results of molecular investigations pointed out that these sections
are consistently associated in well-supported clades (BS = 100%,
PP = 1 0), named Acrolophus–Phalolepis (Garcia-Jacas et al.,
2000). These sections are morphologically similar, and the separation of Acrolophus and Phalolepis is clearly artificial. C. exarata, in
contrast to the other representatives of the group contains guaianes. Its affiliation into the Acrolophus sect. is not also supported
by the recent molecular studies placing it in the section Jacea
(clade Jacea–Lepteranthus), although this inclusion is not supported
by morphological studies. However, the chromosome number of C.
exarata (x = 11) coincides with the basic number found in the Jacea
sect., a fact that justifies its inclusion in this section.
Our results do not seem to support the recognition of Jacea and
Lepteranthus as separate sections and these data are in accordance
with the molecular survey (Garcia-Jacas et al., 2006).
The section Seridia, comprising taxa found exclusively in the
western Mediterranean area, never contain guaianes. On
the other hand the section Solstitiaria has mainly guaianes and
the sections Micrlophus and Chartolepis contain guaianes
exclusively.
The representatives of the sect. Cyanus usually do not contain
sesquiterpenoids. In this study, information about two species of
this section and their sesquiterpenoid profile, characterized by
the presence of guaianes only, is included.
Please cite this article in press as: Bruno, M., et al. Sesquiterpenoids in subtribe Centaureinae (Cass.) Dumort (tribe Cardueae, Asteraceae): Distribution, 13C
NMR spectral data and biological properties. Phytochemistry (2013), http://dx.doi.org/10.1016/j.phytochem.2013.07.002
17
M. Bruno et al. / Phytochemistry xxx (2013) xxx–xxx
Table 5
Elemanes isolated from taxa of the Subtribe Centaureinae.
No
Structure
69
OH
Name
Taxa
Dehydromelitensin
Centaurea
Centaurea
Centaurea
Centaurea
Centaurea
O
HO
Ref.
aegialophila
amara
aspera ssp. stenophylla
aspera ssp. subinermis
castellana
O
C. cineraria ssp. busambarensis
Centaurea cuneifolia
70
8a-hydroxy-15-oxo-5,7aH,6bHelema-1,3,11(13)- trien-12,6-olide
OH
CHO
Centaurea
Centaurea
Centaurea
Centaurea
grisebachii
malacitana
napifolia
paui
Centaurea
Centaurea
Centaurea
Centaurea
pullata
salonitana
sphaerocephala
paui
Bruno et al. (2001)
Gonzalez et al. (1980a)
Picher et al. (1984a)
Cardona et al. (1991)
Gonzalez et al. (1984);Gousiadou and
Skaltsa (2003)
Bruno et al. (1998)
Salan and Öksük (1999), Gousiadou and
Skaltsa (2003)
Djeddi et al. (2008a)
Barrero et al. (1995, 1988)
Bruno et al. (1995)
Cardona et al. (1997), Gousiadou and Skaltsa
(2003)
Gonzalez et al. (1974a, 1977a)
Salan and Öksük (2003)
Bruno et al. (1994)
Cardona et al. (1997), Gousiadou and Skaltsa
(2003)
O
O
71
OAc
HO
dehydromelitensin 8a-acetate
Centaurea bruguierana
Harraz et al. (1994)
dehydromelitensin 8-(20 methylpropanoate)
Centaurea chilensis
Negrete et al. (1993)
dehydromelitensin 8-(20 -methyl-20 propenoate)
Centaurea chilensis
Negrete et al. (1993)
hierapolitanin A
Centaurea hierapolitana
Karamenderes et al. (2007a)
8a-(40 -hydroxy-methacryloyl)dehydromelitensin
Centaurea achaia
Centaurea eryngioides
Centaurea tagananensis
Cheirolophus intybaceus
Skaltsa et al. (2000a), Koukoulitsa et al.
(2002)
Sarg et al. (1989)
Gonzalez et al. (1984), Nowak et al. (1986a)
Marco et al. (1994)
11,13-dehydromelitensin bhydroxyisobutyrate
Centaurea melitensis
Gonzalez et al. (1975, 1977a)
hierapolitanin B
Centaurea hierapolitana
Karamenderes et al. (2007a)
Isoarbutifolin
Centaurea arbutifolia
Gonzalez et al. (1981)
O
O
72
O
O
HO
O
O
73
O
O
HO
74
O
O
OH
O
O
HO
O
O
75
OH
O
O
HO
O
O
76
O
OH
O
HO
77
O
O
OH
OH
O
O
AcO
O
O
78
O
O
HO
O
O
(continued on next page)
Please cite this article in press as: Bruno, M., et al. Sesquiterpenoids in subtribe Centaureinae (Cass.) Dumort (tribe Cardueae, Asteraceae): Distribution, 13C
NMR spectral data and biological properties. Phytochemistry (2013), http://dx.doi.org/10.1016/j.phytochem.2013.07.002
18
M. Bruno et al. / Phytochemistry xxx (2013) xxx–xxx
Table 5 (continued)
No
Structure
79
OH
Name
Taxa
Ref.
8a (50 -hydroxyangeloyl)-11,13dehydromelitensin
Centaurea phrygia
El-Marsy et al. (1985)
8a-(30 ,40 -dihydroxy-20 -methylenebutanoyloxy)- dehydromelitensin;
isocnicin
Centaurea aegialophila
Bruno et al. (2001)
Centaurea attica
Skaltsa et al. (1999), Gousiadou and Skaltsa
(2003)
Marco et al. (1992), Aboul-Ela (1994)
Bruno et al. (1998)
Bruno and Herz (1988), Gousiadou and
Skaltsa (2003)
Salan and Öksük (1999), Gousiadou and
Skaltsa (2003)
Karioti et al. (2002)
Djeddi et al. (2008a)
Trendafilova et al. (2007)
Bruno et al. (1995)
Gousiadou and Skaltsa (2003)
Bruno et al. (2002)
Lazari et al. (2008)
Saroglou et al. (2005)
Skaltsa et al. (2000b), Georgiadou et al.
(2000), Gousiadou and Skaltsa (2003)
Koukoulitsa et al. (2002)
Tsankova et al. (1994)
Karioti et al. (2002)
O
O
O
HO
O
80
O
OH
O
OH
O
HO
Centaurea calcitrapa
Centaurea cinerar. ssp. busambarensis
Centaurea cineraria ssp. umbrosa
O
Centaurea cuneifolia
Centaurea
Centaurea
Centaurea
Centaurea
Centaurea
Centaurea
Centaurea
Centaurea
Centaurea
81
O
OAc
O
OH
8a-(30 -hydroxy-40 -acetoxy-20 methylene-butanoyloxy)dehydromelitensin
Centaurea zuccariniana
Cnicus benedictus
Centaurea deusta
8a-(40 ,50 -dihydroxy-tigloyloxy)11,13-dehydromelitensin
Centaurea achaia
Fortuna et al. (2002)
Bruno et al. (1995)
Lazari et al. (2008)
Bruno et al. (1994)
Skaltsa et al. (2000b), Georgiadou et al.
(2000), Gousiadou and Skaltsa (2003)
Skaltsa et al. (2000a)
8a-(30 ,40 -dihydroxy-20 -methylenebutanoyloxy)-15-oxo-5, 7aH,6bHelema-1,3,11(13)-trien-12,6-olide
Centaurea diffusa
Centaurea paui
Centaurea spinosa
Fortuna et al. (2002)
Cardona et al. (1994)
Saroglou et al. (2005)
Melitensin
Centaurea
Centaurea
Centaurea
Centaurea
Centaurea
amara
aspera ssp. stenophylla
aspera ssp. subinermis
calcitrapa
melitensis
Centaurea
Centaurea
Centaurea
Centaurea
Centaurea
napifolia
nicaensis
pullata
tagananensis
paui
Gonzalez et al. (1980a)
Tortajada et al. (1988), Picher et al. (1984a)
Cardona et al. (1991)
Marco et al. (1992)
Gonzalez et al. (1971, 1975, 1977a, 1978a),
Rybalko et al. (1975)
Bruno et al. (1995)
Medjroubi et al. (2003a)
Djeddi et al. (2008b)
Gonzalez et al. (1984), Nowak et al. (1986a)
Cardona et al. (1997), Gousiadou and Skaltsa
(2003)
Centaurea
Centaurea
Centaurea
Centaurea
Centaurea
O
HO
O
82
OH
O
deusta
grisebachi
moesiaca
napifolia
orphanidea
paniculata ssp. castellana
phyllocephala
spinosa
thessala subsp. drakiensis
diffusa
napifolia
phyllocephala
sphaerocephala
thessala ssp. drakiensis
OH
O
O
HO
O
83
O
OH
O
CHO
OH
O
O
84
OH
O
HO
O
85
OH
CHO
8a-hydroxy-15-oxo-5,7aH,6,11bHelema-1,3-dien- 12,6-olide
O
O
86
OβDglucose
HO
melitensin-8a-O-b-Dglucopyranoside
Centaurea salonitana
Salan and Öksük (2003)
O
O
Please cite this article in press as: Bruno, M., et al. Sesquiterpenoids in subtribe Centaureinae (Cass.) Dumort (tribe Cardueae, Asteraceae): Distribution, 13C
NMR spectral data and biological properties. Phytochemistry (2013), http://dx.doi.org/10.1016/j.phytochem.2013.07.002
19
M. Bruno et al. / Phytochemistry xxx (2013) xxx–xxx
Table 5 (continued)
No
Structure
87
Name
Taxa
Ref.
8-deoxy-11b-hydroxy-melitensin
Centaurea castellana
Gonzalez et al. (1984), Gousiadou and
Skaltsa (2003)
11,13-dihydroisoarbutifolin
Centaurea arbutifolia
Gonzalez et al. (1981)
8a-O-(40 -hydroxy-20 methylenebutanoyloxy)-melitensin
Centaurea pullata
Djeddi et al. (2008b)
Melitensin b-hydroxyisobutyrate
Centaurea melitensis
Gonzalez et al. (1975, 1977a)
5a,6b,7a,8b,11b(H)-15-hydroxy-8(10 ,20 -dihydroxyethyl)-acryloelema1,3-dien-6,12-olide
Centaurea nicaensis
Bruno et al. (1996), Medjroubi et al. (2003a)
Isomelitensin
Centaurea aspera ssp. subinermis
Cardona et al. (1991)
Methyl 8a,6a,15-trihydroxyelema1,3,11(13)-trien-12-oate
Centaurea aspera ssp. subinermis
Cardona et al. (1992)
Elemacarmanin
Centaurea achaia
Skaltsa et al. (2000a), Koukoulitsa et al.
(2002)
Marco et al. (2005)
Marco et al. (1994)
OH
HO
O
O
88
O
O
HO
O
O
89
O
OH
O
HO
O
O
90
O
OH
O
HO
O
O
91
O
OH
O
HO
OH
O
O
92
O
O
HO
OH
93
OH
CO2Me
HO
OH
94
O
OH
Centaurea aspera
Cheirolophus intybaceus
O
CO2Me
HO
OH
OH
O
OH
CO2Me
Methyl 8a-(30 ,40 -dihydroxy-20 methylene-butanoyloxy)-6a,15dihydroxyelema-1,3,11(13)-trien-12oate
OAc
O
OH
CO2Me
Methyl 8a-(30 -hydroxy-40 -acetoxy20 -methylene-butanoyloxy)-6a, 15dihydroxyelema-1,3,11(13)-trien-12oate
95
O
HO
O
Marco et al. (2005)
OH
97
Methyl 8a-O-(40 -acetoxy-50 hydroxyangelate)-6a,15dihydroxyelema-1,3,11(13)-trien-12oate
OH
O
O
CO2Me
HO
Centaurea aspera ssp. stenophylla
Centaurea deusta
Centaurea paui
OH
96
HO
Centaurea spinosa
Centaurea deusta
Skaltsa et al. (1999), Gousiadou and Skaltsa
(2003)
Karioti et al. (2002)
Cardona et al. (1997), Gousiadou and Skaltsa
(2003)
Saroglou et al. (2005)
Karioti et al. (2002)
Centaurea attica
OAc
OH
Our study presents data of the sesquiterpenoids from 16 taxa of
the sect. Acrocentron. This group is defined mainly on the basis of
pollen type, but also by achene characters, involucral bracts morphology and molecular data (ITS spacers of the nuclear ribosomal
DNA). The representatives contain all main types of sesquiterpenoids – germacanes, elemanes, eudesmanes, guaianes.
In order to find further correlations among taxa, based only on
the sesquiterpene composition, a statistical approach was used
(see Supporting information). The cluster analysis of the taxa
belonging to subtribe Centaurinae according to the presence/absence of single sesquiterpenes, carried out by Primer 6 programme
(Clarke and Gorley, 2006), allow us to draw some considerations.
Please cite this article in press as: Bruno, M., et al. Sesquiterpenoids in subtribe Centaureinae (Cass.) Dumort (tribe Cardueae, Asteraceae): Distribution, 13C
NMR spectral data and biological properties. Phytochemistry (2013), http://dx.doi.org/10.1016/j.phytochem.2013.07.002
20
M. Bruno et al. / Phytochemistry xxx (2013) xxx–xxx
Table 6
C NMR data of elemanes.
13
C
69a1
70a2
72a3
73a3
74b4
75a5
76a6
77b4
80a7
83a8
84a9
85a2
89a10
91a9
92a11
93a12
94a13
95a2
97a14
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
10
20
30
40
50
100
200
OCH3
146.1
112.7
114.9
143.9
50.6
78.8
55.0
67.5
49.8
41.9
137.4
169.7
120.5
18.9
67.3
145.5
112.6
137.7
144.8
46.2
77.4
55.0
67.6
49.4
42.0
137.2
n.r.
120.6
18.2
193.6
147.9
113.0
113.3
145.6
51.8
80.0
53.1
70.4
46.2
43.0
139.1
171.4
119.6
19.3
66.7
173.7
35.2
19.1
19.0
147.9
113.0
113.3
145.6
51.7
80.0
53.0
71.0
46.1
42.9
139.1
171.4
119.6
19.3
66.7
167.7
137.4
127.0
18.4
143.8
113.1
112.5
145.1
51.9
78.7
52.3
70.5
42.2
46.3
138.6
169.2
117.8
66.5
65.5
166.2
136.7
125.4
17.7
145.6
113.1
115.1
143.6
50.6
78.6
52.3
69.6
45.0
41.9
136.6
169.2
120.2
18.7
67.3
165.3
139.1
126.7
62.3
145.6
112.6
113.7
143.5⁄
50.2
78.8
51.9
68.8
44.7
41.6
136.3⁄
170.0
120.5
18.2
66.1
174.8
42.1
63.9
13.0
143.8
114.5
116.0
138.2
51.8
78.5
51.2
70.3
41.8
46.4
139.7
169.8
119.5
65.5
66.5
165.5
141.5
124.8
60.3
145.6
113.1
115.1
143.6
50.6
78.7
52.4
69.7
45.0
41.9
136.7c
169.1
120.1
18.4
67.3
165.2
139.0c
71.2
64.8
127.5
144.9
113.1
137.9
144.5
46.1
77.4
52.2
69.6
44.6
42.0
136.4
169.2
120.3
17.9
193.6
165.1
139.0
71.0
65.8
127.5
146.3
112.5
114.5
144.4
50.4
78.7
58.4
68.8
49.4
41.7
41.5
178.6
14.3
18.9
67.3
145.7
112.5
137.4
145.3
46.6
77.3
58.5
69.0
49.3
41.8
41.4
179.0
14.3
18.3
193.5
145.6
112.8
114.6
144.0
50.1
78.2
55.9
70.4
44.8
41.1
40.8
178.1
13.8
18.5
67.1
166.0
136.6
35.0
61.3
127.8
145.8
113.0
114.8
144.1
50.3
78.4
56.0
70.7
44.9
41.6
41.0
177.8
14.1
18.7
67.2
165.3
139.0
71.1
65.7
127.4
146.5
112.4
116.8
145.3
57.6⁄
76.4
57.4⁄
71.3
42.8
n.r.
41.6
179.1
14.3
19.8
67.5
146.9
111.7
114.7
146.6c
55.5
70.7
58.1
67.8
47.1
40.1
138.4c
167.7
128.6
18.7
67.7
146.3
111.9
114.9
146.2
55.3
71.0
54.6
70.9
43.5
40.2
138.0
167.2
128.3
18.3
67.7
165.4
139.4
125.8
62.2
146.2
112.1
114.9
146.2
55.3
70.9
54.7
71.1
43.5
40.2
138.0
167.1
128.4
18.3
67.8
165.2
139.1
71.6
65.7
126.8
52.1
52.0
52.0
146.2
112.1
115.0
146.3
55.3
71.0
54.8
71.4
43.6
40.3
138.0
167.2
128.7
18.3
67.8
164.9
131.4
140.8
63.9
62.9
170.8
20.9
52.1
170.6
21.3
a
b
e
n.r.=not reported. In CDCl3. In DMSO-d6. Inverted with respect to the original paper.
1
Cardona et al. (1989); 2Cardona et al. (1997); 3Negrete et al. (1993); 4Karamenderes et al. (2007a); 5Marco et al. (1994); 6El-Moghazy et al. (2002); 7Bruno and Herz (1988);
Cardona et al. (1994); 9Medjroubi et al. (2003a); 10Djeddi et al. (2008b);11Cardona et al. (1991); 12Cardona et al. (1992); 13Tortajada et al. (1988); 14Marco et al. (2005).
⁄
These values may be interchanged.
8
Two taxa show the lowest grade of resemblance with respect to all
the others: C. solstitialis and C. scoparia both of seventh group.
The Psephellus are divided in two taxonomic groups containing
the same compounds: the first one representing the sect. Psephellus
(Psephellus carthalinicus, Psephellus colchicus, Psephellus daghestanicus, Psephellus dealbatus, Psephellus karabaghensis, Psephellus
nogmovii, Psephellus somcheticus and Psephellus zangezuri) to which
also Psephellus taochius can be added; the second group joining the
sects. Leucophyllae and Hypoleucae (Psephellus leucophyllus, Psephellus declinatus and Psephellus hypoleucus) (Fig. 3).
Although Centaurea phaedopappoides belongs to the Psephellus
group, it is instead correlated by a superimposable occurrence of
the same three compounds with the following taxa: Stemmamarca
rhapontica, Centaurea thracica, Centaurothamnus maximus, Leuzea
rhaponticoides and Leuzea rhapontica ssp.helenipholia. This group
is also close to other four taxa: Stemmamarca carthamoides, Centaurea isaurica, Centaurea janeri and Centaurea marshalliana, the latter
belonging to Psephellus group too.
A close resemblance was found among Centaurea ragusina,
Centaurea sventenii, Centaurea canariensis, Centaurea deflexa and
Amberboa tubiliflora in which almost the same sesquiterpenes
occur (Fig. 3).
Most species of the Acrolophus section is strictly correlated by
cluster analysis and represent the largest group (38 taxa) (Fig. 4),
although this correlation is based on the occurrence of only one
sesquiterpene, cnicin (19), widely diffused in this section. In spite
of this, three taxa, not belonging to the Acrolophus section (Centaurea granatensis, Centaurea raphanina ssp. mixta of the Colymbada
section and Centaurea rocheliana of the Jacea section), are grouped
in this cluster. Other groups are close and they are characterized by
the presence of 19 and/or salonitenolide (4) along with few other
sesquiterpenes. In these clusters, besides taxa of the Acrolophus
section (Centaurea mariolensis, Centaurea monticola, C. exarata), taxa
of the Calcitrapa sect. (Centaurea iberica, Centaurea pontica), Colymbada sect. (Centaurea crocodylium and Centaurea aegialophila), Seridia
sect. (Centaurea eriophora), Jacea sect. (Centaurea weldeniana), Phalolepis sect. (Centaurea alba ssp. caliacrae and C. alba ssp. deusta),
Tetramorphaea sect. ( Centaurea brugueriana) and Rhaponticoides
sect. (Centaurea africana) are represented. All of them have been
classified in the seventh group with the exception of C. africana
belonging to the first group.
Five taxa of the Acrolophus sect. (Centaurea cuneifolia, Centaurea
cineraria ssp. busambarensis, C. cineraria ssp. umbrosa, Centaurea
paniculata ssp. castellana, Centaurea zuccariniana) along with C.
aegialophila (Colymbada sect.) seem to represent a separate cluster
from the other Acrolophus taxa, containing cnicin (19) with other
compounds (69, 80, 104). Other minor groups, correlated by the
same sesquiterpene composition, can be observed in the full dendrogram reported in Supporting information.
On the basis of these observations it seem possible to consider
cnicin (19) and salonitenolide (4), having the same sesquiterpene
skeleton, as markers of Acrolophus section as other authors have already stated (Gousiadou and Skaltsa, 2003).
Starting from this last consideration, we grouped compounds
according to the same sesquiterpene skeleton having the same oxidation state and neglecting any ester side chain occurring (Supporting information). The cluster analysis of this new set of data
discloses new information (Figs. 5 and 6). The groups obtained
by this model were clearly wider and only ones with maximum
similarity are considered. A first cluster of Centaurea grisebachi,
Centaurea orphanidea, Centaurea thessala ssp. drakiensis and C. zuccariniana, all belonging to the Acrolophus section, was obtained.
Two other taxa resulted close to it: Centaurea malacitana and C.
phyllocephala both included in the seventh group as Acrolophus.
The greatest cluster, formed by 56 taxa, includes almost all the
species belonging to the Acrolophus section along with some other
ones of seventh group with the exception of Centaurea derventana
and Centaurea glaberima for which the exact placing in the sections
is not ascertained. Another interesting cluster involves species of
the Acrolophus section and precisely C. grisebachi, C. orphanidea, C.
thessala ssp. drakiensis and C. zuccariniana. These taxa show a peculiarity with respect to the other Acrolophus taxa because they contain not only germacranes but also elemanes and eudesmanes.
Eight taxa of the seventh group are joined in a cluster: four of
Acrolophus (C. cineraria ssp. busambarensis, C. cineraria ssp. umbrosa, C. cuneifolia and C. paniculata ssp. castellana); two of Colymbada
Please cite this article in press as: Bruno, M., et al. Sesquiterpenoids in subtribe Centaureinae (Cass.) Dumort (tribe Cardueae, Asteraceae): Distribution, 13C
NMR spectral data and biological properties. Phytochemistry (2013), http://dx.doi.org/10.1016/j.phytochem.2013.07.002
21
M. Bruno et al. / Phytochemistry xxx (2013) xxx–xxx
Table 7
Eudesmanes isolated from taxa of the Subtribe Centaureinae.
No
Structure
98
H
Name
Taxa
Ref.
b-cyclocostunolide
Centaurea acaulis
Bentamane et al. (2005)
Santamarin
Centaurea acaulis
Centaurea ornata
Centaurea uniflora ssp. nervosa
Bentamane et al. (2005)
Navarro et al. (1990)
Appendino et al. (1986)
Reynosin
Centaurea kurdica
Centaurea uniflora ssp. nervosa
Appendino and Özen (1993)
Appendino et al. (1986)
Sonchucarpolide
Cheirolophus sempervirens
Marco et al. (1994)
Stoebenolide
Centaurea paui
Cardona et al. (1997), Gousiadou
and Skaltsa (2003)
Huneck et al. (1986a)
O
O
99
OH
H
O
O
100
OH
H
O
O
101
OH
H
CHO
O
O
102
OH
Centaurea stoebe
H
CHO
O
O
103
OH
8a-hydroxy-4-epi-sonchucarpolide
Centaurea grisebachi
Centaurea orphanidea
C. thessala ssp. drakiensis
Djeddi et al. (2008a)
Gousiadou and Skaltsa (2003)
Skaltsa et al. (2000b),Georgiadou
et al. (2000), Koukoulitsa et al.
(2002), Gousiadou and Skaltsa
(2003)
8a-hydroxy-sonchucarpolide
Centaurea zuccariniana
Koukoulitsa et al. (2002)
1-hydroxy-8-methacryloxy-15oxoeudesm-11(13)-en-6,12-olide
Centaurea tweediei
Fortuna et al. (2001)
vahlenin
Centaurea hyssopifolia
Gonzalez et al. (1974b, 1977a),
Nowak et al. (1986a)
Gonzalez et al. (1973b, 1978b),
Nowak et al. (1986a)
OH
H
CHO
O
O
104
OH
OH
H
CHO
O
O
105
OH
O
O
H
CHO
O
O
106
OH
Centaurea linifolia
O
O
H
O
O
107
8a-(40 -hydroxy-methacryloyloxy)4-epi-sonchucarpolide
Centaurea achaia
Skaltsa et al. (2000a)
OH
OH
8a-(40 -hydroxy-methacryloyloxy)sonchucarpolide
Centaurea achaia
Cheirolophus x hortigenus
Skaltsa et al. (2000a)
Marco et al. (1994)
OH
O
O
H
CHO
O
O
108
OH
O
O
H
CHO
O
O
(continued on next page)
Please cite this article in press as: Bruno, M., et al. Sesquiterpenoids in subtribe Centaureinae (Cass.) Dumort (tribe Cardueae, Asteraceae): Distribution, 13C
NMR spectral data and biological properties. Phytochemistry (2013), http://dx.doi.org/10.1016/j.phytochem.2013.07.002
22
M. Bruno et al. / Phytochemistry xxx (2013) xxx–xxx
Table 7 (continued)
No
Structure
109
OH
O
Taxa
Ref.
Centaurea attica
Skaltsa et al. (2000b), Gousiadou
and Skaltsa (2003)
Djeddi et al. (2008a)
Barrero et al. (1997a)
Trendafilova et al. (2007)
Gousiadou and Skaltsa (2003)
Lazari et al. (2008)
Saroglou et al. (2005)
Georgiadou et al. (2000), Gousiadou
and Skaltsa (2003)
OH
O
H
CHO
Name
Malacitanolide
Centaurea grisebachi
Centaurea malacitana
Centaurea moesiaca
Centaurea orphanidea
Centaurea phyllocephala
Centaurea spinosa
Cent. thessala ssp. drakiensis
OH
O
O
110
OH
O
Centaurea grisebachi
Centaurea spinosa
Djeddi et al. (2008a)
Saroglou et al. (2005)
8a-(30 -hydroxy-40 -acetoxy-20 methylene-butanoyloxy)-4- episonchucarpolide; 40 -acetylmalacitanolide
Centaurea attica
Skaltsa et al. (2000b)
Centaurea deusta
Koukoulitsa et al. (2002), Karioti
et al. (2002)
Djeddi et al. (2008a)
Trendafilova et al. (2007)
Gousiadou and Skaltsa (2003)
Saroglou et al. (2005)
Koukoulitsa et al., 2002, Karioti
et al. (2002)
OH
O
H
CHO
4-epi-malacitanolide
OH
O
O
111
OH
O
OAc
O
H
CHO
OH
O
O
112
OH
O
OAc
O
H
CHO
OH
8a-(30 -hydroxy-40 -acetoxy-20 methylene-butanoyloxy)sonchucarpolide; 40 -acetyl-4-epimalacitanolide
Centaurea
Centaurea
Centaurea
Centaurea
Centaurea
grisebachi
moesiaca
orphanidea
spinosa
deusta
Centaurea grisebachi
Djeddi et al. (2008a)
8a-O-(40 -acetoxy-20 -hydroxymethylbuten-20 -oyloxy)-4-episonchucarpolide
Centaurea spinosa
Saroglou et al. (2005)
4a-hydroxy-8a-O-(40 -acetoxy-50 hydroxyangelate)-11(13)eudesmen-12,6a-15,1b-diolide
Centaurea aspera ssp. subinermis
Cardona et al. (1991)
8a-hydroxy-11b,13-dihydroonopordaldehyde
Centaurea granata
Centaurea pullata
Medjroubi et al. (1998)
Djeddi et al. (2008b)
4a,8a-dihydroxy-11bH-eudesma12,6a-15, 1b-diolide
Centaurea aspera ssp. subinermis
Cardona et al. (1991)
8a-hydroxy-11b,13-4-episonchucarpolide
Centaurea pullata
Djeddi et al. (2008b)
8a-O-(40 -hydroxy-20 -methylenebutanoyloxy)-11b,13dihydrosonchucarpolide
Centaurea pullata
Djeddi et al. (2007)
8a-O-(40 -hydroxy-20 -methylenebutanoyloxy)-11b,13- dihydro-4epi -sonchucarpolide
Centaurea pullata
Djeddi et al. (2007)
O
O
113
OH
OH
O
OAc
O
H
CHO
O
O
114
OH
H
O
O
O
O
H
OH
OAc
O
O
115
OH
H
CHO
O
O
116
H
OH
O
O
H
OH
O
O
117
OH
OH
H
CHO
O
O
118
OH
O
OH
O
H
CHO
O
O
119
OH
O
OH
O
H
CHO
O
O
Please cite this article in press as: Bruno, M., et al. Sesquiterpenoids in subtribe Centaureinae (Cass.) Dumort (tribe Cardueae, Asteraceae): Distribution, 13C
NMR spectral data and biological properties. Phytochemistry (2013), http://dx.doi.org/10.1016/j.phytochem.2013.07.002
23
M. Bruno et al. / Phytochemistry xxx (2013) xxx–xxx
Table 7 (continued)
No
Structure
120
OH
H
Name
Taxa
Ref.
11-epi-dihydroreynosin
Centaurea ornata
Navarro et al. (1990)
Alantolactone
Serratula latifolia
Rustaiyan and Feramarzi (1988)
Ivalin
Centaurea cadmea
Serratula latifolia
Karamenderes et al. (2007b)
Rustaiyan and Feramarzi (1988)
Isocostic acid; 12-carboxy3,11(13)-eudesmadiene
Cheirolophus mauritanicus
Marco et al. (1994)
Costic acid
Cheirolophus mauritanicus
Serratula latifolia
Marco et al. (1994)
Rustaiyan and Feramarzi (1988)
4-epi-illicic acid
Cherirolophus mauritanicus
Marco et al. (1994)
3-oxo-1,2-dehydrocostic acid
Cheirolophus x hortigenus
Cherirolophus sempervirens
Marco et al. (1994)
Marco et al. (1994)
3-oxo-1,2-dehydrocostic acid
methyl ester
Centaurea arguta
Gadeschi et al. (1989)
3-hydroxy-1,2-dehydrocostic acid
Centaurea canariensis ssp.
subexpinnata
Cheirolophus sempervirens
Bohlmann and Gupta (1981)
3-hydroxy-1,2-dehydrocostic acid
methyl ester
Centaurea arguta
Gadeschi et al. (1989)
Hierapolitanin C
Centaurea hierapolitana
Karamenderes et al. (2007a)
Hierapolitanin D
Centaurea hierapolitana
Karamenderes et al. (2007a)
1b,6a-dihydroxy-4(15)-eudesmene
Centaurea conifera (Leuzea conifera)
Fernandez et al. (1995)
Pterodontriol D
Centaurea pamphylica
Shoeb et al. (2007b)
Rhaponticol
Rhaponticum uniflorum
Cheng et al. (1995), Wei et al.
(1997), Zhang et al. (2010)
1b,4a,6a,15-tetrahydroxyeudesmane
Centaurea aspera ssp. subinermis
Cardona et al. (1992)
O
O
121
O
O
122
HO
O
O
H
123
CO2H
H
124
CO2H
H
125
CO2H
H
HO
126
O
CO2H
H
127
O
CO2Me
H
128
HO
CO2H
H
129
HO
CO2Me
H
130
Marco et al. (1994)
OH
O
HO
HO
131
O
H
OH
CO2H
OH
O
HO
HO
132
O
OH
HO
OH
H
133
CO2H
OH
OH
H
HO
H
OH
134
OH
OH
H
135
OH
OH
HOH2C
H
OH
OH
(continued on next page)
Please cite this article in press as: Bruno, M., et al. Sesquiterpenoids in subtribe Centaureinae (Cass.) Dumort (tribe Cardueae, Asteraceae): Distribution, 13C
NMR spectral data and biological properties. Phytochemistry (2013), http://dx.doi.org/10.1016/j.phytochem.2013.07.002
24
M. Bruno et al. / Phytochemistry xxx (2013) xxx–xxx
Table 7 (continued)
No
136
Structure
OH
O
Name
Taxa
Ref.
Methyl 1,6-dihydroxy-8methacryloxyeudesm-11(13)-en15-oic acid-12-oate
Centaurea tweediei
Fortuna et al. (2001)
4-epi-carmanin
Centaurea achaia
Skaltsa et al. (2000a)
atticin
Centaurea attica
Skaltsa et al. (2000b)
4,5-dioxo-10-epi-4,5-seco-ceudesmol-20 -O-acetyl-b-Dfucopyranoside
Phonus arborescens
Barrero et al. (1997b)
10-epi-c-eudesmol-b-Dfucopyranoside
Phonus arborescens
Barrero et al. (1997b)
10-epi-c-eudesmol-20 -O-acetyl-b-
Phonus arborescens
Barrero et al. (1997b)
O
COOMe
H
OH
COOH
137
OH
O
O
CO2Me
H
CHO OH
138
OH
OH
O
H
CHO OH
OAc
O
OH
COOMe
139
OH
O
O
O
O
OH
AcO
140
OH
O
O
OH
HO
141
OH
D-fucopyranoside
O
O
OH
AcO
(C. aegialophila and Centaurea eryngioides); one of Jacea (Centaurea
phrygia) and one of Tetramorphea (C. brugueriana). The separation
of Psephellus in two groups is still effective in this model but other
species are involved. This time, the taxa belonging to the Psephellus
group (Psephellus sect.) are joined with Chartolepis biebersteinii,
Centaurea hermannii and also with C. phaedopappoides, S. rhapontica, C. thracica, C. maximus, L. rhaponticoides, L. rhapontica ssp.helenipholia that, in the previous single compound analysis, resulted
rather separated from the Psephellus group. The others Psephellus
taxa (sects. Leucophyllae and Hypoleucae) are grouped with Cheirolophus junoniaus, Cheirolophus teydis, Cheirolophus uliginosus, Cheirolophus sventenii, Centaurea americana, C. canariensis, all belonging to
first group as Psephellus, with Centaurea collina, Centaurea ptosimopappoides, Centaurea kotschy, C. ragusina, Centaurea debeauxii
ssp. thuillieri (all of seventh group) and with Amberboa divaricata,
Centaurea pabotii and Tricholepis glaberrima.
Finally, using this model, Centaurea aspera ssp. subinermis, C.
paui and Acroptilon repens are the taxa showing the lowest resemblance in this subtribe.
4. Biological activity
4.1. Antimicrobial
Antimicrobial activity of cynoropicrin (162) was screened using
22 strains including Gram+ and Gram bacteria and the yeasts
Candida albicans and Candida tropicalis. The MIC varied from 100
to 2500 lg/mL, against the strains of bacteria and yeasts evaluated
(Schinor et al., 2004). Antibacterial activity against Staphylococcus
aureus, Escherichia coli and Pseudomonas aeruginosa was also demonstrated (Modonova et al., 1986). Cnicin (19) and cynaropicrin
(162) have been identified as potent, irreversible inhibitors of the
bacterial enzyme MurA of E. coli and P. aeruginosa showing an activity comparable to fosfomycin expecially for the latter bacterial
strain (IC50 = 10.5 lM). They covalently bind the thiol group of
Cys115 and their unsaturated ester side chain has pivotal impor-
tance for the inhibition of MurA. These results provided evidence
that MurA is a target protein of sesquiterpene lactones (SLs), which
is probably highly relevant for their known antibacterial effect
(Bachelier et al., 2006).
Further studies established the structure of the antibacterial
target enzyme MurA in complex with its substrate UNAG (UDPN-acytilglucosamine) and its potent inhibitor cnicin (19) by Xray. The structure reveals that MurA has catalyzed the formation
of a covalent adduct between cnicin and UNAG. This adduct,
formed by an unusual ‘‘anti-Michael’’ 1,3-addition of UNAG to an
a,b-unsaturated carbonyl side chain of cnicin, inhibits MurA
(Steinbach et al., 2008).
Cnicin (19) has bactericidal activity against Bordetella bronchiseptica, P. aeruginosa, S. aureus, Brucella abortus (Karawya et al.,
1975; Vanhaelen-Fastre, 1972) and, starting from salonitenolide
(4), several esters have been prepared. Cnicin (19), salonitenolide
(4), the elemane 80 and several synthetic compounds were tested
for their antibacterial activity against Bacillus cereus, Bacillus subtilis, P. aeruginosa, S. aureus, Streptococcus faecalis, E. coli, Proteus mirabilis and Salmonella typhi. The 8,15-diesters showed a good activity
(MIC = 6.25–12.5 lg/mL), comparable with that of cnicin (19)
(MIC = 3.12–12.5 lg/mL). The 15-monoester compounds were not
very active indicating that esterification at the C-8 position is an
important structural feature for antibacterial properties (Bruno
et al., 2003).
Compounds 19, 21, 23,80, 83, 95, 109, 110, 111 and 113 isolated
from Centaurea spinosa, were tested in vitro against three Gram+
and three Gram bacteria. They were all inactive against tested
Gram bacteria whereas compounds 83, 110 and 113 showed an
activity against Micrococcus flavus from four to six times higher
than streptomycin (MIC = 0.6, 0.6 and 0.4 lg/mL, respectively)
and compounds 19, 21, 23, 80 and 83 showed a moderate activity
against B. cereus (Saroglou et al., 2005). Also compound 32 exhibited moderate antibacterial activity only toward Gram+ bacteria
(Suleimenov et al., 2005b). Compounds 36, 44, 45, 46, 84, 89,
115, 117, 118 and 119, isolated from Centaurea pullata, were tested
Please cite this article in press as: Bruno, M., et al. Sesquiterpenoids in subtribe Centaureinae (Cass.) Dumort (tribe Cardueae, Asteraceae): Distribution, 13C
NMR spectral data and biological properties. Phytochemistry (2013), http://dx.doi.org/10.1016/j.phytochem.2013.07.002
C
98a1
99a1
100a1
101e2
103a3
104a4
107a5
108b6
109c7
110a8
111a3
112a9
113a8
114a10
115b11
116a10
117a5
118a12
119a12
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
10
20
30
40
50
100
200
41.9
21.7
39.8
144.4
55.1
80.1
50.1
22.9
36.0
38.7
139.7
170.7
116.5
18.1
109.2
75.2
32.8
121.3
133.4
52.2
81.5
51.0
21.2
34.3
40.9
139.1
171.0
116.6
11.0
23.2
78.3
31.4
33.6
142.5
53.1
79.6
49.7
21.5
35.8
43.0
139.4
170.5
116.6
11.6
110.6
79.6
29.2
24.9
48.7
48.9
83.2
50.0
23.2
37.3
41.9
140.0
170.9
116.8
21.2
203.3
76.4
25.6
20.6
43.8
46.7
74.4
55.0
65.8
47.3
41.2
136.5
172.5
119.2
11.8
200.1
77.1
24.3
28.3
47.7
48.2
78.8
55.5
67.4
47.2
40.7
136.8
170.8
120.8
13.0
202.6
78.0
27.2
22.4
44.9
48.9
76.1
53.8
69.9
43.9
41.5
136.3
169.2
120.5
13.9
201.8
165.2
139.0
126.7
62.3
76.4
24.3
27.6
47.6
48.0
78.9
52.6
69.5
42.5
40.7
136.0
169.0
120.3
12.6
203.3
165.3
139.4
126.0
61.0
75.9
26.7
21.8
44.7
47.2
76.0
52.3
69.5
43.4
41.0
137.5
169.3
118.7
13.4
203.7
165.2
141.9
70.2
65.4
125.3
76.9
24.6
23.1
47.8
48.1
78.8
55.3
69.5
43.5
41.9
136.6
170.2
120.2
12.8
202.2
166.5
76.3
27.6
22.6
47.5h
48.2
78.6
52.7
69.8
43.6h
40.8
136.0
169.2
120.4
14.1
201.8
164.6
138.3
69.7
67.1
127.6
171.4
20.8
77.8
27.8
23.1
46.0
48.4
76.1
54.0
70.5
44.2
41.9
136.6
169.6
121.2
15.6
211.0
165.1
130.6
138.6
63.3
62.5
171.1
20.5
76.0⁄
30.2
38.5
n.r.
57.3#
74.2⁄
51.5#
69.1⁄
42.7
n.r.
135.4
n.r.
120.0
13.2
n.r.
n.r.
n.r.
141.5
63.2
62.5
n.r.
20.8
26.1
19.3
40.4
48.9
48.4
79.2
59.2
68.3
51.5
35.1
41.2
178.0
14.3
19.3
203.2
76.3⁄
30.3
38.6
n.r.
57.7#
74.0⁄
57.3#
68.3⁄
46.9
n.r.
40.5
n.r.
14.3
13.5
n.r.
78.2
27.3
22.4
45.1
48.6
76.0
59.8
68.9
48.3
41.2
41.7
178.5
14.3
14.2
202.1
71.5
65.9
127.6
78.0
27.1
22.7
44.9
48.8
76.1
53.7
69.7
43.8
41.5
136.4
171.5
120.8
13.9
201.9
164.7
138.3
69.7
67.1
128.1
171.5g
n.r.
76.9
28.1
24.1
47.6
47.7
78.1
56.3
70.3
42.3
40.5
40.3
176.3
13.8
12.7
202.0
166.1
136.6
35.1
61.3
128.3
77.7
27.6
23.6
45.0
48.4
75.7
56.9
70.1
43.5
40.8
40.1
177.4
13.8
13.9
201.7
165.9
137.0
35.1
61.4
127.3
C
120n:r:
13
121a2
122e14
123a15
124a1
125a6
126a16
128a16
130f17
131f17
132a18
133e19
133f20
134a21
135a22
137a23
138a3
139d24
140a24
141d24
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
10
20
30
40
50
60
100
200
OCH3
78.5
31.5
36.2
143.0
53.2
78.3
48.3
20.4
33.7
42.8
38.8
179.9
9.7
11.7
110.5
41.0
22.2
36.8
41.1
133.0
122.3
46.3
77.0
42.2
34.3
142.1
170.6
119.9
17.2
17.6
41.2
66.3
47.5
147.3
45.7
27.6
40.6
76.8
51.9
34.1
142.8
170.0
119.5
19.1
108.2
27.3
22.8
121.0
134.6
46.7
40.0
40.1
37.7
29.3
32.2
145.1
172.0
125.0
15.5
21.0
41.8
23.4
41.1
145.3
49.9
27.4
39.4
30.0
36.8
35.9
150.5
172.2
124.6
16.3
105.4
43.8
18.0
41.4⁄
72.2
51.8
27.5
40.1
26.4
41.2⁄
33.7
145.2
172.2
124.9
18.7
30.1
161.2
126.9
189.3
145.5
47.9
26.8
38.5
28.8
36.8
37.5
145.2
171.9
125.6
17.8
118.2
141.6
127.1
70.7
150.2
47.5
28.7
39.2
29.2
37.7
37.8
145.2
172.2
125.2
19.2
104.6
35.9
27.5
81.6
151.0
44.3
29.8
39.8
27.1
40.7
35.5
147.0
169.9
121.5
15.3
108.5
101.4
74.0
77.2
70.3
76.4
61.4
34.0
27.5
82.1
72.2
48.7
26.1
40.6
23.0
44.3
33.7
147.1
170.0
121.2
18.0
20.1
101.5
73.7
76.9
70.4
76.8
61.5
49.0
31.9
35.1
146.2
55.9
67.0
49.3
18.2
36.3
41.7
26.0
16.2
21.1
11.6
107.8
79.3
29.4
36.7
72.7
47.9
73.1
51.2
23.4
41.4
41.5
25.9
24.5
25.1
14.7
22.6
76.6
29.5
32.0
69.0
47.9
73.1
51.2
24.7
34.0
34.0
28.8
24.8
29.1
14.1
22.7
36.0
22.9
37.0
146.9
43.3
41.2
77.1
70.2
43.4
37.0
153.4
64.6
114.7
16.6
105.5
80.5
28.0⁄
29.6⁄
n.r.
57.6
75.6
51.8
22.3⁄
39.7⁄
39.1
29.6
18.5#
20.7#
12.8#
80.4
77.1
27.8
24.0
48.5
50.8
70.9
55.9
70.5
41.3
38.8
137.2
166.9
129.3
12.0
202.7
165.2
139.1
125.9
62.3
78.0
26.7
22.3
45.0
48.8
76.2
53.9
70.3
44.0
n.r.
n.r
n.r.
128.7
11.9
203.6
n.r.
n.r.
69.6
67.4
127.6
18.6
36.8
43.6
208.0
214.8
39.8
50.4
21.9
39.2
48.3
78.6
23.1
22.0
25.4
29.8
96.0
73.4
72.6
73.0
70.8
16.9
170.2
21.2
38.8
19.1
32.2
134.7
124.9
38.3
44.4
21.9
24.8
34.2
81.2
26.8
26.2
19.7
23.3
97.2
71.7
72.1
74.1
70.3
16.6
39.6
19.7
32.7
134.9
125.1
38.8
45.0
22.8
25.4
34.5
80.6
27.2
25.7
19.8
23.2
95.8
73.5
72.6
73.2
70.6
16.9
170.1
21.2
⁄
g
52.1
n.r.
20.6
52.1
M. Bruno et al. / Phytochemistry xxx (2013) xxx–xxx
n.r. = not reported.
a
In CDCl3. b In CDCl3/MeOD. c In DMSO-d6. d In acetone–d6. e In pyridine-d5. f In CD3OD. g Amended with respect to the original paper. hAmended by authors [Z. Naturforsch. C. , (2004), 59c, 612]. ⁄, ,# These values may be
interchanged. 1Yang et al., 1997; 2Buděšinský and Šaman (1995); 3Skaltsa et al., 2000b; 4Koukoulitsa et al. (2002); 5Lazari et al., 1998; 6Marco et al. (1994); 7Barrero et al., 1997a; 8Saroglou et al. (2005); 9Karioti et al., 2002;
10
Cardona et al. (1991); 11Medjroubi et al., 1998; 12Djeddi et al., 2007; 13Navarro et al., 1990; 14Karamenderes et al., 2007b; 15Fontana et al. (2007); 16Al-Sheddi et al., 2002; 17Karamenderes et al., 2007a; 18Su et al., 1995; 19Zhao,
1997; 20Shoeb et al., 2007b; 21Wei et al., 1997; 22Cardona et al., 1992; 23Skaltsa et al., 2000a; 24Barrero et al., 1997b.
25
Please cite this article in press as: Bruno, M., et al. Sesquiterpenoids in subtribe Centaureinae (Cass.) Dumort (tribe Cardueae, Asteraceae): Distribution, 13C
NMR spectral data and biological properties. Phytochemistry (2013), http://dx.doi.org/10.1016/j.phytochem.2013.07.002
Table 8
C NMR data of eudesmanes.
13
26
M. Bruno et al. / Phytochemistry xxx (2013) xxx–xxx
Table 9
Guaianes isolated from taxa of the Subtribe Centaureinae.
No
Structure
142
H
Name
Taxa
Ref.
Dehydrocostus lactone
Centaurea chilensis
Negrete et al. (1984)
8a-hydroxy-dehydrocostus
lactone
Centaurea canariensis ssp. subexpin.
Centaurea chilensis
Cheirolophus x hortigenus
Cheirolophus sempervirens
Bohlmann and Gupta (1981), Nowak et al.
(1986a)
Negrete et al. (1984)
Marco et al. (1994)
Marco et al. (1994)
Centaurea chilensis
Negrete et al. (1988a)
Centaurea floccosa
Negrete et al. (1988a)
8a-methacryloyloxydehydrocostus lactone
Centaurea canariensis ssp. subexpin.
Bohlmann and Gupta (1981), Nowak et al.
(1986a)
Subexpinnatin; 3desoxycynaropicrin
Centaurea canariensis ssp. subexpin.
Bohlmann and Gupta (1981), Gonzalez et al.
(1982), Gonzalez Collado et al. (1986a)
zaluzanin C
Centaurea ptosimopappa
Cheirolophus x hortigenus
Cheirolophus sempervirens
Çelik et al. (2006)
Marco et al. (1994)
Marco et al. (1994)
Zaluzanin D
Centaurea acaulis
Centaurea ptosimopappa
Bentamane et al. (2005)
Çelik et al. (2006)
H
O
O
143
H
OH
H
O
O
144
8a-acetoxy-dehydrocostus
lactone
H
OAc
H
O
O
145
H
O
H
O
O
O
146
H
O
H
OH
O
O
O
147
H
HO
H
O
O
148
H
AcO
H
O
O
149
H
HO
OH
Acroptilon repens
Desacylcynaropicrin; 8hydroxyzaluzanin C; 8desacylsauprin; deacylaguerin A
Amberboa muricata
H
O
Amberboa tubiliflora
O
Centaurea aegyptiaca
Centaurea behen
Centaurea
Centaurea
Centaurea
Centaurea
canariensis
canariensis ssp. subexpin.
chilensis
clementei
Centaurea
Centaurea
Centaurea
Centaurea
Centaurea
Centaurea
Centaurea
Centaurea
Centaurea
collina
deflexa
floccosa
kotschyi
linifolia
ornata
ptosimopappa
ragusina
scoparia
Zha and Hou (2008)
Gonzalez et al. (1973b, 1977a), Khan et al.
(2010)
Omar et al. (1983), Ahmed et al. (1990), Khan
et al. (2010)
Sarg et al. (1987)
Rustaiyan et al. (1981a),Ohno et al.
(1973),Nowak et al. (1986a)
Gonzalez et al. (1977a, 1978c,a, 1980b)
Gonzalez et al. (1977a, 1978c,a, 1980b)
Negrete et al. (1988a)
Gonzalez et al. (1977a), Massanet et al.
(1983), Nowak et al. (1986a), Gonzalez
Collado et al. (1986a)
Fernandez et al. (1989)
Chicca et al. (2011)
Negrete et al. (1988a)
Öksüz and Putun (1983)
Gonzalez et al. (1977a), Nowak et al. (1986a)
Bastos et al. (1994)
Çelik et al. (2006)
Mahmoud et al. (1986)
Youssef and Frahm (1994b), Helal et al.
(1997)
Please cite this article in press as: Bruno, M., et al. Sesquiterpenoids in subtribe Centaureinae (Cass.) Dumort (tribe Cardueae, Asteraceae): Distribution, 13C
NMR spectral data and biological properties. Phytochemistry (2013), http://dx.doi.org/10.1016/j.phytochem.2013.07.002
27
M. Bruno et al. / Phytochemistry xxx (2013) xxx–xxx
Table 9 (continued)
No
Structure
150
Name
Kandavanolide
H
AcO
OH
Taxa
Ref.
Centaurea solstitialis
Centaurea sventenii
Centaurea tagananensis
Cheirolophus x hortigenus
Cheirolophus junoniaus
Cheirolophus mauritanicus
Cheirolophus uliginosus
Grossheimia macrocephala
Gonzalez et al. (1983), Jakupovic et al. (1986)
Gonzalez et al. (1977a)
Gonzalez et al. (1984), Nowak et al. (1986a)
Marco et al. (1994)
Gonzalez et al. (1993)
Marco et al. (1994)
Marco et al. (1994)
Barbetti et al. (1985), Piacentini et al. (1986),
Piacentini et al., 1987
Bentamane et al. (2005)
Rustaiyan and Ardebili (1984)
Vajs et al. (1999)
Daniewski et al. (1993), Nowak et al. (1996)
Centaurea
Centaurea
Centaurea
Centaurea
acaulis
kandavanensis
nicolai
salonitana
H
O
O
151 HO
OH
H
2a,9b-dihydroxy-dehydrocostus Acroptilon repens
lactone
Zhao et al. (2006)
salograviolide B
Centaurea nicolai
Centaurea salonitana
Vajs et al. (1999)
Daniewski et al. (1993), Nowak et al. (1996)
3-deacetyl-9-O-acetylsalograviolide A
Centaurea nicolai
Vajs et al. (1999)
H
O
O
152
O
H
AcO
OH
H
O
O
153
OAc
H
HO
OH
H
O
O
154
HO CH Cl
2
H
14-chloro-10-b-hydroxy-10(14)- Centaurea acaulis
dihydrozaluzanin D
Bentamane et al. (2005)
9-acetylsalograviolide A
Centaurea nicolai
Vajs et al. (1999)
Salograviolide A; 9bhydroxykandavanolide
Centaurea ainetensis
Ghantous et al. (2008), El-Najjar et al. (2008),
Al-Saghir et al. (2009)
Rustaiyan and Ardebili (1984)
Vajs et al. (1999)
Daniewski et al. (1992), Rychlewska et al.
(1992), Nowak et al. (1996)
AcO
H
O
O
155
OAc
H
AcO
OH
H
O
O
156
OH
H
AcO
Centaurea kandavanensis
Centaurea nicolai
Centaurea salonitana
OH
H
O
O
157
H
HO
40 -nor-20 -methoxy-cynaropicrin
Grossheimia macrocephala
Barbetti et al. (1985)
Aguerin A
Centaurea arbutifolia
Centaurea canariensis
Centaurea pabotii
Centaurea salonitana
Cheirolophus junoniaus
Cheirolophus mauritanicus
Cheirolophus metlesicsii
Cheriolophus sempervirens
Cheirolophus teydis
Gonzalez et al. (1981)
Gonzalez et al. (1977a, 1978c)
Marco et al. (1992)
Daniewski et al. (1993)
Gonzalez et al. (1993)
Marco et al. (1994)
Gonzalez et al. (1993)
Marco et al. (1994)
Gonzalez et al. (1993)
O
OCH3
H
O
O
O
158
H
HO
O
H
O
O
O
(continued on next page)
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NMR spectral data and biological properties. Phytochemistry (2013), http://dx.doi.org/10.1016/j.phytochem.2013.07.002
28
M. Bruno et al. / Phytochemistry xxx (2013) xxx–xxx
Table 9 (continued)
No
Structure
159
H
AcO
Name
Taxa
Ref.
Acetylaguerin A
Cheirolophus metlesicsii
Gonzalez et al. (1993)
Aguerin B; aaguerin b
Acroptilon repens
Amberboa tubuliflora
Centaurea arguta
Centaurea behen
Stevens (1982), Nowak et al. (1986a)
Ahmed et al. (1990)a, Khan et al. (2010)
Gadeschi et al. (1989)
Rustaiyan et al. (1981a), Öksüz et al. (1982),
Nowak et al. (1986a)
Gonzalez et al. (1977a, 1978c)
Gonzalez et al. (1977a, 1978c, 1982),
Gonzalez Collado et al. (1986a)
Chicca et al. (2011)
Gonzalez et al. (1977a, 1978c,b), Nowak et al.
(1986a)
Medjroubi et al. (2005)
Mahmoud et al. (1986)
Bruno et al. (1991b)
Gonzalez et al. (1977a, 1978c)
Öksük and Topçu (1994)
Marco et al. (1994)
Gonzalez et al. (1993)
Marco et al. (1994)
Barbetti et al. (1985)
Cis et al. (2006), Zhang et al. (2010)
Huneck and Knapp (1986)
Nowak (1993a,b);Nowak et al. (1996)
Daniewski et al. (1993)a; Nowak et al. (1996)
Jakupovic et al. (1986)
Nowak et al. (1986b,a, 1996);Nowak (1992)
Nowak et al. (1986b, 1996), Nowak (1992)
Nowak et al. (1986b, 1996), Nowak (1992)
Nowak et al. (1986b,a, 1996), Nowak (1992)
Nowak et al. (1986b,a, 1996), Nowak (1992)
Nowak et al. (1986b, 1996), Nowak (1992)
Nowak et al. (1986b, 1996), Nowak (1992)
Nowak et al. (1986b,a, 1996), Nowak (1990,
1992)
Nowak (1992), Nowak et al. (1996)
Nowak et al. (1986b, 1996), Nowak (1992)
Nowak et al. (1986b)
Nowak et al. (1986b,a, 1996), Nowak (1992)
Huneck and Knapp (1986)
Stevens (1982), Jakupovic et al. (1986),
Nowak et al. (1986a), Zhao et al. (2006), Zha
and Hou (2008)
Forgacs et al. (1981), Rojatkar et al. (1997)
Gonzalez et al. (1973b, 1977a), Nowak et al.
(1986a), Khan et al. (2010)
Harrison and Kulshreshtha (1984), Khan
et al. (2010)
Omar et al. (1983), Ahmed et al. (1990), Khan
et al. (2010)
Nowak (1992), Nowak et al. (1996)
El Dahmy et al. (1985)
Gonzalez et al. (1977a), Nowak et al. (1986a)
Ohno et al. (1973), Nowak et al. (1986a)
Gadeschi et al. (1989)
Rustaiyan et al. (1981a), Öksüz et al. (1982),
Nowak et al. (1986a)
Nowak (1992, 1993a,b), Daniewski and
Nowak (1993)
Gonzalez et al. (1977a), Massanet et al.
(1983), Nowak et al. (1986a), Gonzalez
Collado et al. (1986a)
Gonzalez et al. (1977a, 1978c,a, 1980b)
Gonzalez et al. (1977a), Gonzalez Collado
et al. (1985, 1986a), Nowak et al. (1986a)
Geppert et al. (1983), Nowak et al. (1986a)
Chicca et al. (2011)
O
H
O
O
O
160
H
HO
O
H
O
O
Centaurea canariensis
Centaurea canariensis ssp. subexpin.
O
Centaurea deflexa
Centaurea linifolia
161
Centaurea musimomum
Centaurea ragusina
Centaurea solstitialis ssp. schouwii
Centaurea sventenii
Chartolepis glastifolia
Cheirolophus x hortigenus
Cheirolophus teydis
Cheirolophus uliginosus
Grossheimia macrocephala
Rhaponticum pulchrum
Rhaponticum uniflorum
15-deoxyrepin; salograviolide C Centaurea bella
Centaurea salonitana
Centaurea solstitialis
Psephellus carthalinicus
a
The stereochemistry of the side Psephellus colchicus
Psephellus daghestanicus
chain was not indicated in the
original paper. Here it is given on Psephellus dealbatus
Psephellus declinatus
the basis of the NMR values.
Psephellus hypoleucus
Psephellus karabaghensis
Psephellus leucophyllus
H
HO
O
O
H
O
O
O
162
cynaropicrin; sauprin
H
HO
O
H
OH
O
O
O
Psephellus nogmovii
Psephellus somcheticus
Psephellus taochius
Psephellus zangezuri
Rhaponticum uniflorum
Acroptilon repens
Amberboa divaricata
Amberboa muricata
Amberboa ramosa
Amberboa tubuliflora
Centaurea
Centaurea
Centaurea
Centaurea
Centaurea
Centaurea
adjarica
aegyptiaca
africana
americana
arguta
behen
Centaurea bella
Centaurea clementei
Centaurea canariensis
Centaurea canariensis ssp. subexpin.
Centaurea debeauxii ssp. thuillieri
Centaurea deflexa
Please cite this article in press as: Bruno, M., et al. Sesquiterpenoids in subtribe Centaureinae (Cass.) Dumort (tribe Cardueae, Asteraceae): Distribution, 13C
NMR spectral data and biological properties. Phytochemistry (2013), http://dx.doi.org/10.1016/j.phytochem.2013.07.002
29
M. Bruno et al. / Phytochemistry xxx (2013) xxx–xxx
Table 9 (continued)
No
Structure
Name
Taxa
Ref.
Centaurea exarata
Nowak et al. (1986a), Gousiadou and Skaltsa
(2003)
Yayli et al. (2006)
Öksük et al. (1994)
Rosselli et al. (2006a)
Nowak et al. (1986a)
Öksüz and Putun (1983)
Gonzalez et al. (1977a), Nowak et al. (1986a)
Medjroubi et al. (2005)
Bastos et al. (1994)
Nowak et al. (1986a, 1989a, 1996), Nowak
(1992)
Çelik et al. (2006)
Öksük and Serin (1997)
Mahmoud et al. (1986)
Kaminskii et al. (2010a), Kaminskii et al.
(2010b), Kaminskii et al., 2010c, Kaminskii
et al. (2011)
Dawidar et al. (1989), Youssef and Frahm
(1994b)
Bruno et al. (1991b)
Gonzalez et al. (1983), Merrill and Stevens
(1985), Jakupovic et al. (1986), Wang et al.
(1991), Hamburger et al. (1991), Cheng et al.
(1992), Hay et al. (1994), Tešević et al.
(1998b)
Gonzalez et al. (1977a)
Gonzalez et al. (1984), Nowak et al. (1986a)
Nowak et al. (1986a, 1989a, 1996),Nowak
(1992)
Muhammad et al. (2003)
Nowak et al. (1986c, 1996),Nowak (1992)
Nowak et al. (1986a,c, 1996), Nowak (1992)
Nowak et al. (1986a,c, 1996), Nowak (1992)
Nowak et al. (1986c, 1996), Nowak (1992)
Marco et al. (1994)
Gonzalez et al. (1993)
Marco et al. (1994)
Marco et al. (1994)
Gonzalez et al. (1993)
Marco et al. (1994)
Daniewski et al. (1982), Barbetti et al. (1985),
Nowak et al. (1986a), Piacentini et al. (1986),
Piacentini et al., 1987
Nowak et al. (1988), Nowak (1992)
Nowak et al. (1988, 1996), Nowak (1992)
Nowak et al. (1986b,a, 1996), Nowak (1992)
Nowak (1992), Nowak et al. (1996)
Nowak (1992), Nowak et al. (1996)
Nowak et al. (1986b,a, 1996), Nowak (1992)
Nowak et al. (1986b,a, 1996), Nowak (1992)
Nowak et al. (1986b, 1996), Nowak (1992)
Nowak (1992), Nowak et al. (1996)
Nowak et al. (1986b,a, 1996), Nowak (1992)
Nowak (1992), Nowak et al. (1996)
Nowak (1992), Nowak et al. (1996)
Nowak et al. (1986b,a, 1996), Nowak (1992)
Cis et al. (2006), Zhang et al. (2010)
Nowak et al. (1986a), Berdin et al. (1999)
Huneck and Knapp (1986)
Nowak et al. (1986a, 1988, 1996), Nowak
(1990, 1992), Sorova et al. (2008), Kokoska
and Janovska (2009)
Nowak et al. (1986a, 1996)
Singhal et al. (1982), Nowak et al. (1986a),
Bhattacharyya et al. (1996)
Serkerov and Aleskerova (1982)
Centaurea
Centaurea
Centaurea
Centaurea
Centaurea
Centaurea
Centaurea
Centaurea
Centaurea
helenoides
hermannii
hololeuca
hyssopifolia
kotschyi
linifolia
musimomum
ornata
phaeopappoides
Centaurea
Centaurea
Centaurea
Centaurea
ptosimopappa
ptosimopappoides
ragusina
scabiosa
Centaurea scoparia
Centaurea solstitialis sspschouwii
Centaurea solstitialis
Centaurea sventenii
Centaurea tagananensis
Centaurea thracica
Centaurothamnus maximus
Chartolepis bieberstenii
Chartolepis glastifolia
Chartolepis intermedia
Chartolepis pterocaula
Cheirolophus x hortigenus
Cheirolophus junoniaus
Cheirolophus mauritanicus
Cheirolophus sempervirens
Cheirolophus teydis
Cheirolophus uliginosus
Grossheimia macrocephala
Leuzea rhapontica ssp. helenifolia
Leuzea rhaponticoides
Psephellus carthalinicus
Psephellus colchicus
Psephellus daghestanicus
Psephellus dealbatus
Psephellus declinatus
Psephellus hypoleucus
Psephellus karabaghensis
Psephellus leucophyllus
Psephellus nogmovii
Psephellus somcheticus
Psephellus zangezuri
Rhaponticum pulchrum
Rhaponticum serratuloides
Rhaponticum uniflorum
Stemmamarca carthamoides
Stemmamarca rhapontica
Tricholepis glaberrima
163 HO
acroptin
H
O
H
Acroptilon repens
OH
O
O
O
(continued on next page)
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NMR spectral data and biological properties. Phytochemistry (2013), http://dx.doi.org/10.1016/j.phytochem.2013.07.002
30
M. Bruno et al. / Phytochemistry xxx (2013) xxx–xxx
Table 9 (continued)
No
Structure
164
H
Cl
HO
Taxa
Ref.
Centaurea kotschyi
Centaurea linifolia
Psephellus nogmovii
Psephellus somcheticus
Psephellus taochius
Psephellus zangezuri
Centaurea paboti
Cheirolophus mauritanicus
Öksüz and Putun (1983), Gürkan et al. (1998)
Gonzalez et al. (1977a, 1978b), Nowak et al.
(1986a)
Medjroubi et al. (2005)
Nowak et al. (1996)
Jakupovic et al. (1986), Tešević et al. (1998b)
Nowak et al. (1986b,a, 1996), Nowak (1992)
Nowak et al. (1986b, 1996), Nowak (1992)
Nowak et al. (1986b, 1996), Nowak (1992)
Nowak et al. (1986b,a, 1996), Nowak (1992)
Nowak et al. (1986b,a, 1996), Nowak (1992)
Nowak et al. (1986b, 1996), Nowak (1992)
Nowak et al. (1986b, 1996),Nowak (1992)
Nowak et al. (1986b,a, 1996), Nowak (1990,
1992)
Nowak (1992), Nowak et al. (1996)
Nowak et al. (1986b, 1996), Nowak (1992)
Nowak et al. (1986b)
Nowak et al. (1986b,a, 1996), Nowak (1992)
Marco et al., 1992
Marco et al. (1994)
Centaurea collina
Centaurea ornata
Fernandez et al. (1987)a, 1989a
Navarro et al., 1990
OH
O
H
Name
Linichlorin B
Centaurea musimomum
Centaurea salonitana
Centaurea solstitialis
Psephellus carthalinicus
Psephellus colchicus
Psephellus daghestanicus
Psephellus dealbatus
Psephellus declinatus
Psephellus hypoleucus
Psephellus karabaghensis
Psephellus leucophyllus
O
O
O
165
Deacylcynaropicrin 8-O-[(S)-30 hydroxy-20 -methylpropionate]
H
HO
O
H
OH
O
O
O
166
H
(2’S)-17,18-dihydroxy-aguerin
A; 3a-dihydro-4(15)dehydrogrosshemin-a,bdihydroxyisobutyrate
OH
HO
OH
O
H
O
O
O
167
H
a
The side chain reported in the
original paper has been
amended
(20 R)-17,18-dihydroxy-aguerin A Centaurea kotschyi
OH
HO
OH
O
H
Öksüz and Putun (1983)
O
O
O
168
H
HO
O
H
(1S,3S,5R,6R,7R,8S)-8-tigloyloxy- Centaurea scoparia
3-hydroxyguai4(15),10(14),11(13)-triene-6,12olide
Helal et al. (1997)
Cebellin F
Centaurea scoparia
Chartolepis glastifolia
Nowak et al. (1986d, 1989a, 1996, 1992)
Nowak et al. (1986d, 1996), Nowak (1990,
1992, 1993a,b)
Helal et al. (1997)
Nowak et al. (1986c, 1996)
8a-hydroxy-3b-(benzoyloxy)1aH,5aH,6bH,7aH-guai4(15),10(14),11(13)-trien-6,12olide
Centaurea scoparia
Youssef (1998)
3b,8a-O-di-(40 -hydroxytygloyl)1aH, 5aH,6bH,7aH-guai4(15),10(14),11(13)-triene-6,
12-olide
Centaurea scoparia
Helal et al. (1997)
O
O
O
169
H
HO
Centaurea adjarica
Centaurea bella
O
OH
H
O
O
O
170
O
H
O
OH
H
O
O
171
H
O
OH
O
O
H
O
O
HO
O
Please cite this article in press as: Bruno, M., et al. Sesquiterpenoids in subtribe Centaureinae (Cass.) Dumort (tribe Cardueae, Asteraceae): Distribution, 13C
NMR spectral data and biological properties. Phytochemistry (2013), http://dx.doi.org/10.1016/j.phytochem.2013.07.002
31
M. Bruno et al. / Phytochemistry xxx (2013) xxx–xxx
Table 9 (continued)
No
Structure
172
O
O
Name
Taxa
Ref.
Cebellin K
Centaurea bella
Nowak (1992, 1993a,b), Nowak et al. (1996)
Cebellin N
Centaurea bella
Daniewski and Nowak (1993), Nowak
(1993a,b), Nowak et al. (1996)
Cebellin L
Centaurea bella
Nowak (1992, 1993a,b), Nowak et al. (1996)
Cebellin O
Centaurea bella
Daniewski and Nowak (1993), Nowak
(1993a,b), Nowak et al. (1996)
Repdiolide
Acroptilon repens
Centaurea adjarica
Centaurea bella
Stevens (1982), Nowak et al. (1986a)
Nowak et al. (1989a, 1996), Nowak (1992)
Nowak et al. (1986d, 1996), Nowak (1990,
1992, 1993a,b)
Cis et al. (2006), Zhang et al. (2010)
Berdin et al. (2001)
Nowak et al. (1988, 1996), Nowak (1992),
Kokoska and Janovska (2009)
Rustaiyan et al. (1981b), Rustaiyan and
Nazarians (1984)
H
OH
H
O
O
173
O
O
H
OH
H
O
O
174
O
O
H
HO
H
O
O
175
O
O
H
HO
H
O
O
176
HO
H
HO
O
H
Rhaponticum pulchrum
Rhaponticum serratuloides
Stemmacantha carthamoides
O
O
O
177
HO
H
HO
O
H
2,3-dihydroxy-8methacryloyloxydehydrocostuslactone
Acroptilon repens
Cebellin B
Centaurea bella
Nowak et al. (1986d, 1996), Nowak (1990,
1992, 1993a,b)
Cebellin A
Centaurea bella
Nowak et al. (1986d, 1996), Nowak (1990,
1992, 1993a,b)
3-Desoxysolstitialin A
Centaurea imperialis
Rustaiyan et al. (1984)
O
O
O
178
O
O
H
HO
OH
H
O
O
179
O
O
H
HO
OH
H
O
O
180
H
OH OH
H
O
O
(continued on next page)
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NMR spectral data and biological properties. Phytochemistry (2013), http://dx.doi.org/10.1016/j.phytochem.2013.07.002
32
M. Bruno et al. / Phytochemistry xxx (2013) xxx–xxx
Table 9 (continued)
No
Structure
181
Name
Taxa
Ref.
Solstitialin A
Centaurea depressa
Centaurea imperialis
Centaurea solstitialis
Akkol et al. (2009)
Rustaiyan et al. (1984)
Thiessen et al. (1969), Thiessen and Hope
(1970), Rybalko et al. (1975), Gonzalez et al.
(1977a, 1983), Sakakibara et al. (1977),
Merrill and Stevens (1985), Naidenova et al.
(1988), Wang et al. (1991), Hamburger et al.
(1991), Cheng et al. (1992), Tešević et al.
(1998b), Yesilada et al. (2004), Gürbüz and
Yesilada (2007), Akkol et al. (2009)
3-Acetylsolstitialin A
Centaurea solstitialis
Wang et al. (1991), Hamburger et al. (1991),
Cheng et al. (1992)
13-Acetylsolstitialin A
Centaurea
Centaurea
Centaurea
Centaurea
Subexpinnatin C
Centaurea canariensis ssp. subexpin.
Gürkan et al. (1998)
Akkol et al. (2009)
Rustaiyan et al. (1984)
Zarghami and Heinz (1969), Gonzalez et al.
(1977a, 1983), Wang et al. (1991),
Hamburger et al. (1991), Cheng et al. (1992),
Hay et al. (1994), Tešević et al. (1998b),
Yesilada et al. (2004), Gürbuz et al. (2006),
Gürbüz and Yesilada (2007), Akkol et al.
(2009),Ozcelik et al. (2009)
Gonzalez Collado et al. (1985, 1986a)
Subexpinnatin B
Centaurea canariensis ssp. subexpin.
Gonzalez Collado et al. (1985, 1986a)
OH
Clementein B
Centaurea clementei
Gonzalez Collado et al. (1986b,a)
OH
Clementein
Centaurea clementei
Massanet et al. (1983), Gonzalez Collado
et al. (1986b,a)
8a-hydroxy-11b-13Hdehydrocostus lactone
Amberboa ramosa
Centaurea canariensis ssp. subexpin.
Khan (2004)
Bohlmann and Gupta (1981), Nowak et al.
(1986a)
3-epi-11,13-dihydrodeacylcynaropicrin
Amberboa ramosa
Centaurea canariensis ssp. subexpin.
Khan (2004), Khan et al. (2010)
Gonzalez Collado et al. (1985, 1986a)
H
HO
OH OH
H
O
O
182
H
AcO
OH OH
H
O
O
183
H
HO
OH OAc
H
behen
depressa
imperialis
solstitialis
O
O
184
H
OH
H
O
O
O
185
O
H
OH
O
H
O
O
O
186
O
H
HO
O
H
O
O
O
187
O
H
HO
O
H
O
O
O
188
H
OH
H
O
O
189
O
H
HO
OH
H
O
O
Please cite this article in press as: Bruno, M., et al. Sesquiterpenoids in subtribe Centaureinae (Cass.) Dumort (tribe Cardueae, Asteraceae): Distribution, 13C
NMR spectral data and biological properties. Phytochemistry (2013), http://dx.doi.org/10.1016/j.phytochem.2013.07.002
33
M. Bruno et al. / Phytochemistry xxx (2013) xxx–xxx
Table 9 (continued)
No
Structure
Name
Taxa
Ref.
HO
11b,13-dihydrodeacylcynaropicrin; 11bH11,13-dihydro-deacylaguerin A
Amberboa ramosa
Centaurea canariensis ssp. subexpin.
Centaurea collina
Centaurea paboti
Centaurea ptosimopappa
Centaurea ptosimopappoides
Centaurea salonitana
Centaurea solstitialis
Cheirolophus junoniaus
Cheirolophus mauritanicus
Cheirolophus metlesicsii
Cheirolophus teydis
Cheirolophus uliginosus
Tricholepis glaberrima
Khan et al. (2005a), Ibrahim et al. (2010)
Gonzalez Collado et al. (1985, 1986a)
Fernandez et al. (1989)
Marco et al., 1992
Çelik et al. (2006)
Öksük and Serin (1997)
Salan and Öksük (2003)
Tešević et al. (1998b)
Gonzalez et al. (1993)
Marco et al. (1994)
Gonzalez et al. (1993)
Gonzalez et al. (1993)
Marco et al. (1994)
Singhal et al., 1982
11bH-11,13-dihydro-aguerin A
Cheirolophus mauritanicus
Cheirolophus metlesicsii
Marco et al. (1994)
Gonzalez et al. (1993)
deacylcynaropicrin 8-O-[(S)-3hydroxy-2-methylpropionate]
Cheirolophus mauritanicus
Marco et al. (1994)
11b,13-dihydroaguerin B
Cheirolophus uliginosus
Marco et al. (1994)
11b,13-dihydrocynaropicrin
Cheirolophus uliginosus
Marco et al. (1994)
Deacylcynaropicrin 8-O-(2S,3dihydroxy-2-methylpropionate)
Centaurea collina
Fernandez et al., 1987a, 1989a
11bH-11,13dihydrodesacylcynaropicrin-8b-D-glucoside; 3b-hydroxy11b,13-dihydro-8a-O-b -Dglucozaluzanin C
Centaurea chilensis
Negrete et al. (1988b)
190
H
OH
H
O
O
191
H
HO
O
H
O
O
O
192
H
HO
O
H
OH
O
O
O
193
H
HO
O
H
O
O
O
194
H
HO
O
H
OH
O
O
O
195
H
OH
HO
OH
O
H
O
O
O
196
H
HO
O-β-D-glucoside
H
O
O
197
H
OCH3
HO
O
H
O
O
OCH3
Centaurea scoparia
3b-hydroxy-8a-(30 ,40 dimethoxybenzoyloxy)-11b, 13dihydro-1aH,5aH,6bH,7aHguai-4(15), 10(14)-dien-6,12olide
Youssef (1998)
8a-hydroxy-11a-13Hdehydrocostus lactone
Khan et al. (2005a, 2010)
O
198
H
Amberboa ramosa
OH
H
O
O
(continued on next page)
Please cite this article in press as: Bruno, M., et al. Sesquiterpenoids in subtribe Centaureinae (Cass.) Dumort (tribe Cardueae, Asteraceae): Distribution, 13C
NMR spectral data and biological properties. Phytochemistry (2013), http://dx.doi.org/10.1016/j.phytochem.2013.07.002
34
M. Bruno et al. / Phytochemistry xxx (2013) xxx–xxx
Table 9 (continued)
No
Structure
199
H
HO
OH
H
O
Name
Taxa
Ref.
8a-hydroxy-11a,13dihydrozaluzanin C; 11aH11,13-dihydro-deacylaguerin A;
11a,13-dihydrodeacylcynaropicrin
Centaurea aegyptiaca
Centaurea ptosimopappa
El Dahmy et al. (1985)
Çelik et al. (2006)
Centaurea scoparia
Cheirolophus metlesicsii
Centaurea salonitana
Centaurea sinaica
Helal et al. (1997), Kakuda et al. (1998)
Gonzalez et al. (1993)
Salan and Öksük (2003)
Al-Easa et al. (1990)
11a,13-dihydro-8amethacryloyloxy-zaluzanin C
Leuzea longifolia
Santos et al. (1988)
11a,13-dihydro-8a-(20 hydroxymethyl)-acryloyloxyzaluzanin C
Leuzea longifolia
Santos et al. (1988)
11a,13-dihydro-3bmethacryloyloxy-zaluzanin C
Leuzea longifolia
Santos et al. (1988)
11a,13-dihydro-3bmethacryloyloxy-zaluzanin C
Leuzea longifolia
Santos et al. (1988)
O
200
sinaicin
H
AcO
OH
H
O
O
201
H
HO
O
H
O
O
O
202
H
HO
O
H
OH
O
O
O
203
H
O
OH
H
O
O
OH
O
204
H
O
OH
H
O
O
O
205
H
HO
8a-hydroxy-11a,13-dihydro-13- Acroptilon repens
N-pyrrolidin-zaluzanin C;
Zha and Hou (2008)
8-desacylrepin
Centaurea aegyptiaca
Centaurea scoparia
Centaurea solstitialis
Sarg et al. (1987)
Helal et al. (1997)
Jakupovic et al. (1986)
8-deacyloxy-8a(methylacryloxy)-subteolide;
19-desoxyjanerin; 17,18desoxyrepin
Centaurea adjarica
Centaurea bella
Nowak et al. (1996)
Daniewski and Nowak (1993), Nowak
(1993a,b), Nowak et al. (1996)
Massiot et al. (1986)
Medjroubi et al. (2005)
Jakupovic et al. (1986)
Öksük and Topçu (1994)
Cis et al. (2006), Zhang et al. (2010)
Stevens (1982), Rustaiyan and Nazarians
(1984), Nowak et al. (1986a), Jakupovic et al.
(1986)
Nowak et al. (1986d, 1989a, 1996), Nowak
(1992)
Sarg et al. (1987)
Bruno et al. (2005a)
OH
H
O
N
O
206
H
HO
OH
O
H
O
O
207
H
HO
O
O
H
O
O
O
208
Janerin
H
HO
O
O
H
OH
Centaurea incana
Centaurea musimomum
Centaurea solstitialis
Chartolepis glastifolia
Rhaponticum pulchrum
Acroptilon repens
Centaurea adjarica
O
O
O
Centaurea aegyptiaca
Centaurea babylonica
Please cite this article in press as: Bruno, M., et al. Sesquiterpenoids in subtribe Centaureinae (Cass.) Dumort (tribe Cardueae, Asteraceae): Distribution, 13C
NMR spectral data and biological properties. Phytochemistry (2013), http://dx.doi.org/10.1016/j.phytochem.2013.07.002
35
M. Bruno et al. / Phytochemistry xxx (2013) xxx–xxx
Table 9 (continued)
No
Structure
Name
Taxa
Ref.
Centaurea bella
Geppert et al. (1983), Nowak et al. (1986d,
1996), Nowak (1990, 1992, 1993a,b)
Bruno et al. (1998)
Öksük et al. (1994)
Rosselli et al. (2006)°
Massiot et al. (1986)
Flamini et al., 2004
Gonzalez et al. (1977a,b)
Nowak et al. (1989a, 1996), Nowak (1992)
Medjroubi et al. (2005)
Nowak et al. (1986a, 1989a, 1996), Nowak
(1992)
Çelik et al. (2006)
Youssef and Frahm (1994b)
Sarg et al. (1988)
Merrill and Stevens (1985)
Nowak et al. (1989a, 1996), Nowak (1992)
Appendino et al. (1986)
Muhammad et al. (2003)
Nowak et al. (1986c, 1996), Nowak (1992)
Nowak et al. (1986a,c, 1996), Nowak (1992)
Nowak et al. (1986c, 1996), Nowak (1992)
Nowak et al. (1988, 1992)
Nowak et al. (1988, 1996), Nowak (1992)
Nowak et al. (1986b,a, 1996), Nowak (1992)
Nowak et al., 1986b, 1996, Nowak (1992)
Nowak et al. (1986c, 1996), Nowak (1992)
Nowak et al. (1986b,a, 1996), Nowak (1992)
Nowak et al. (1986b, 1996), Nowak (1992)
Nowak (1992), Nowak et al. (1996)
Nowak et al. (1986b, 1996), Nowak (1992)
Nowak et al. (1986b)
Nowak et al. (1986b,a, 1996), Nowak (1992)
Cis et al. (2006), Zhang et al. (2010)
Nowak et al. (1988, 1996), Nowak (1992),
Kokoska and Janovska (2009)
Nowak et al. (1996)
Evstratova et al., 1966;Rybalko et al. (1975),
Gonzalez et al. (1977a), Rustaiyan et al.
(1981b), Stevens (1982), Mallabaev et al.
(1982), Rustaiyan and Nazarians (1984),
Nowak et al. (1986a), Stevens et al. (1990),
Robles et al. (1997)
Nowak et al. (1989a, 1996), Nowak (1992)
Sarg et al. (1987)
Bruno et al. (2005a)
Geppert et al. (1983), Nowak et al. (1986d,
1996), Nowak (1990, 1992, 1993a,b)
Bruno et al. (1998)
Rosselli et al. (2006a)
Evstratova et al. (1969, 1972), Rybalko et al.
(1975), Gonzalez et al. (1977a)
Medjroubi et al. (2005)
Kaminskii et al., 2010b, Krasnov et al. (2011)
Merrill and Stevens (1985), Jakupovic et al.
(1986), Hamburger et al. (1993)
Nowak et al. (1986c, 1996), Nowak (1992)
Nowak et al. (1986a,c, 1996), Nowak (1992)
Nowak et al. (1986c, 1996), Nowak (1992)
Nowak et al. (1986b,a, 1996), Nowak (1992)
Nowak et al. (1986b, 1996), Nowak (1992)
Nowak et al. (1986b, 1996), Nowak (1992)
Nowak et al. (1986b,a, 1996), Nowak (1992)
Nowak et al. (1986b, 1996), Nowak (1992)
Nowak (1992), Nowak et al. (1996)
Nowak et al. (1986b, 1996), Nowak (1992)
Nowak et al. (1986b)
Nowak et al. (1986b,a, 1996), Nowak (1992)
Bruno et al. (1998)
Massiot et al. (1986)
Merrill and Stevens (1985), Hamburger et al.,
1993
Centaurea
Centaurea
Centaurea
Centaurea
Centaurea
Centaurea
Centaurea
Centaurea
Centaurea
conifera (=Leuzea conifera)
hermannii
hololeuca
incana
isaurica
janeri
marshalliana
musimomum
phaeopappoides
Centaurea ptosimopappa
Centaurea scoparia
Centaurea sinaica
Centaurea solstitialis
Centaurea thracica
Centaurea uniflora ssp. nervosa
Centaurothamnus maximus
Chartolepis bieberstenii
Chartolepis glastifolia
Chartolepis pterocaula
Leuza rhapontica ssp. helenifolia
Leuzea rhaponticoides
Psephellus carthalinicus
Psephellus colchicus
Psephellus daghestanicus
Psephellus dealbatus
Psephellus karabaghensis
Psephellus nogmovii
Psephellus somcheticus
Psephellus taochius
Psephellus zangezuri
Rhaponticum pulchrum
Stemmamarca carthamoides
209
Repin
H
HO
O
O
O
H
Stemmamarca rhapontica
Acroptilon repens
O
O
Centaurea
Centaurea
Centaurea
Centaurea
O
adjarica
aegyptiaca
babylonica
bella
Centaurea conifera (=Leuzea conifera)
Centaurea hololeuca
Centaurea hyrcanica
Centaurea musimomum
Centaurea scabiosa
Centaurea solstitialis
210
subluteolide
H
HO
O
O
O
H
Chartolepis bieberstenii
Chartolepis glastifolia
Chartolepis pterocaula
Psephellus carthalinicus
Psephellus colchicus
Psephellus daghestanicus
Psephellus dealbatus
Psephellus karabaghensis
Psephellus nogmovii
Psephellus somcheticus
Psephellus taochius
Psephellus zangezuri
Centaurea conifera (=Leuzea conifera)
Centaurea incana
Centaurea solstitialis
O
O
O
(continued on next page)
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NMR spectral data and biological properties. Phytochemistry (2013), http://dx.doi.org/10.1016/j.phytochem.2013.07.002
36
M. Bruno et al. / Phytochemistry xxx (2013) xxx–xxx
Table 9 (continued)
No
Structure
211
H
OH
HO
H
Taxa
Ref.
Centaurea babylonica
Bruno et al. (2005a)
Chlorohyssopifolin C; acroptilin
Acroptilon repens
Centaurea scoparia
Centaurea uniflora ssp. nervosa
Evstratova et al., 1967, 1971, 1973, Gonzalez
et al. (1977a), Rustaiyan et al. (1981b),
Mallabaev et al., 1982, Rustaiyan and
Nazarians (1984)
Nowak et al. (1986d, 1989a, 1996), Nowak
(1992)
Bruno et al. (2005a)
Geppert et al. (1983), Nowak et al. (1986d,
1996), Nowak (1990, 1992, 1993a,b)
Evstratova et al., 1972, Rybalko et al. (1975),
Gonzalez et al. (1977a)
Gonzalez et al., 1974b, 1977a, Nowak et al.
(1986a)
Massiot et al. (1986)
Gonzalez et al. (1977a, 1978b), Nowak et al.
(1986a)
Nowak et al. (1989a, 1996), Nowak (1992)
Merrill and Stevens (1985), Jakupovic et al.
(1986)
Nowak et al. (1986c, 1996), Nowak (1992)
Nowak et al. (1986a,c, 1996), Nowak (1992)
Nowak et al. (1986c, 1996), Nowak (1992)
Nowak et al. (1986b,a, 1996), Nowak (1992)
Nowak et al. (1986b, 1996), Nowak (1992)
Nowak et al. (1986b, 1996), Nowak (1992)
Nowak et al. (1986b,a, 1996), Nowak (1992)
Nowak et al. (1986b, 1996), Nowak (1992)
Nowak (1992), Nowak et al. (1996)
Nowak et al. (1986b, 1996), Nowak (1992)
Nowak et al. (1986b)
Nowak et al. (1986b,a, 1996), Nowak (1992)
Berdin et al. (1999)
Nowak (1992)
Nowak et al. (1986d, 1993a,b), Nowak et al.
(1996)
Helal et al. (1997)
Appendino et al. (1986)
epoxyrepdiolide
Acroptilon repens
Centaurea aegyptiaca
Stevens (1982), Nowak et al. (1986a)
Sarg et al. (1987)
8a-tigloyloxy-2a,3b-dihydroxy4a- epoxydehydrocostulactone
Centaurea uniflora ssp. nervosa
Appendino et al. (1986)
Cebellin I
Centaurea adjarica
Nowak et al., 1986d, 1989a, 1996, Nowak
(1992)
Nowak et al. (1986d, 1996), Nowak (1990,
1992, 1993a,b)
OH
O
O
Name
Babylin A
O
O
O
212
H
Cl
HO
OH
O
O
H
Centaurea adjarica
O
O
Centaurea babylonica
Centaurea bella
O
Centaurea hyrcanica
Centaurea hyssopifolia
Centaurea incana
Centaurea linifolia
Centaurea marshalliana
Centaurea solstitialis
213
cebellin P
H
HO
Chartolepis bieberstenii
Chartolepis glastifolia
Chartolepis pterocaula
Psephellus carthalinicus
Psephellus colchicus
Psephellus daghestanicus
Psephellus dealbatus
Psephellus karabaghensis
Psephellus nogmovii
Psephellus somcheticus
Psephellus taochius
Psephellus zangezuri
Rhaponticum serratuloides
Centaurea adjarica
Centaurea bella
O
O
OH
H
O
O
O
214
HO
H
HO
O
O
H
O
O
O
215
HO
H
HO
O
O
H
O
O
O
216
HO
HO
Centaurea bella
O
O
H
O
O
O
217
Chlorohyssopifolin B
H
HO
HO
Cl
OH
H
Amberboa ramosa
Centaurea aegyptiaca
Centaurea hyssopifolia
Centaurea linifolia
O
O
Centaurea scoparia
Khan (2004, 2010)
El Dahmy et al. (1985)
Gonzalez et al. (1972a, 1977a), Rybalko et al.
(1975), Nowak et al. (1986a)
Gonzalez et al. (1977a, 1978b), Nowak et al.
(1986a)
Youssef and Frahm, 1994a, Helal et al. (1997)
Please cite this article in press as: Bruno, M., et al. Sesquiterpenoids in subtribe Centaureinae (Cass.) Dumort (tribe Cardueae, Asteraceae): Distribution, 13C
NMR spectral data and biological properties. Phytochemistry (2013), http://dx.doi.org/10.1016/j.phytochem.2013.07.002
37
M. Bruno et al. / Phytochemistry xxx (2013) xxx–xxx
Table 9 (continued)
No
Structure
218
H
HO
HO
Cl
Name
Taxa
Ref.
19-deoxychlorojanerin;
linochlorin A; elegin
Acroptilon repens
Mallabaev et al., 1982, Jakupovic et al. (1986)
Centaurea adjarica
Centaurea aegyptiaca
Centaurea bella
Nowak et al. (1996)
El Dahmy et al. (1985)
Daniewski and Nowak (1993), Nowak
(1993a,b), Nowak et al. (1996)
Öksük et al. (1994)
Gonzalez et al. (1977a, 1978b), Nowak et al.
(1986a)
Medjroubi et al. (2005)
Dawidar et al., 1989
Tešević et al. (1998b)
Öksük and Topçu (1994)
Jakupovic et al. (1986)
Khan (2004), Khan et al. (2005a, 2010)
Nowak et al. (1989a, 1996), Nowak (1992)
El Dahmy et al. (1985)
Nowak et al. (1986d, 1996), Nowak (1990,
1992, 1993a,b)
Fernandez et al. (1995)
Öksük et al. (1994)
Gonzalez et al. (1977a,b)
Nowak et al. (1989a, 1996), Nowak (1992)
Medjroubi et al. (2005)
Nowak et al. (1989a, 1996), Nowak (1992)
Çelik et al. (2006)
Dawidar et al., 1989, Youssef and Frahm
(1994a), Mattern et al., 1996
Sarg et al. (1988)
Yesilada et al. (2004), Gürbuz et al. (2006),
Gürbüz and Yesilada (2007), Ozcelik et al.
(2009)
Nowak et al. (1989a, 1996), Nowak (1992)
Muhammad et al. (2003)
Nowak et al. (1986c, 1996), Nowak (1992)
Nowak et al. (1986a,c, 1996), Nowak (1992)
Nowak et al. (1986c, 1996), Nowak (1992)
Nowak et al., 1988, Nowak (1992)
Nowak et al. (1988, 1996), Nowak (1992)
Cis et al. (2006), Zhang et al. (2010)
Nowak et al. (1988, 1996), Nowak (1992),
Kokoska and Janovska (2009)
Nowak et al. (1996)
O
H
O
O
Centaurea hermannii
Centaurea linifolia
O
219
Chlorojanerin; cebellin C
H
HO
HO
Cl
O
H
OH
O
O
Centaurea musimomum
Centaurea scoparia
Centaurea solstitialis
Chartolepis glastifolia
Acroptilon repens
Amberboa ramosa
Centaurea adjarica
Centaurea aegyptiaca
Centaurea bella
Centaurea
Centaurea
Centaurea
Centaurea
Centaurea
Centaurea
Centaurea
Centaurea
O
conifera (=Leuzea conifera)
hermannii
janeri
marshalliana
musimomum
phaeopappoides
ptosimopappa
scoparia
Centaurea sinaica
Centaurea solstitialis
Centaurea thracica
Centaurothamnus maximus
Chartolepis bieberstenii
Chartolepis glastifolia
Chartolepis pterocaula
Leuza rhapontica ssp. helenifolia
Leuzea rhaponticoides
Rhaponticum pulchrum
Stemmamarca carthamoides
Stemmamarca rhapontica
220
Khan et al., 2004a, 2010
O
Amberboa ramosa
4b-(chloromethyl)-3b,4adihydroxy,8a- [(S)-3-hydroxy-2methyl-propionyloxy]-1aH,5aH,
6bH,7aH-guaia-10(14),11(13)dien-6,12-olide
Amberboa ramosa
Khan et al., 2004a, 2010
O
4b-(chloromethyl)-3b,4adihydroxy,8a- [(S)-2carboxypropionoxy]1aH,5aH,6bH, 7aH-guaia10(14),11(13)- dien-6,12-olide
17,18-epoxy-19-deoxychlorojanerin; solstiziolide
Centaurea adjarica
Nowak (1992), Nowak et al. (1996)
Centaurea aegyptiaca
Centaurea bella
Centaurea solstitialis
El Dahmy et al. (1985)
Nowak (1992, 1993a,b), Nowak et al. (1996)
Merrill and Stevens (1985), Jakupovic et al.
(1986)
Centaurea incana
Centaurea solstitialis
Chartolepis glastifolia
Massiot et al. (1986)
Merrill and Stevens (1985)
Öksük and Topçu (1994)
H
HO
HO
Cl
O
H
O
OH
O
221
H
HO
HO
Cl
O
COOH
H
O
O
222
H
HO
HO
Cl
O
O
H
O
O
O
223
epi-solstiziolide
H
HO
HO
Cl
O
O
H
O
O
O
(continued on next page)
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NMR spectral data and biological properties. Phytochemistry (2013), http://dx.doi.org/10.1016/j.phytochem.2013.07.002
38
M. Bruno et al. / Phytochemistry xxx (2013) xxx–xxx
Table 9 (continued)
No
Structure
224
H
Cl
HO
HO
Cl
Taxa
Ref.
Acroptilon repens
Harley-Mason et al. (1972), Gonzalez et al.
(1977a), Cassady et al. (1979), Rustaiyan
et al. (1981b), Mallabaev et al. (1982),
Rustaiyan and Nazarians (1984)
Nowak et al. (1989a, 1996), Nowak (1992)
El Dahmy et al. (1985)
Nowak et al. (1986d, 1996), Nowak (1990,
1992, 1993a,b)
Fernandez et al., 1995
Evstratova et al., 1972, Rybalko et al. (1975)
Gonzalez et al. (1972a, 1977a), Rybalko et al.
(1975), Nowak et al. (1986a)
Rustaiyan et al. (1984)
Gonzalez et al. (1977a, 1978b), Nowak et al.
(1986a)
Medjroubi et al. (2005)
Gonzalez et al. (1974a, ?), Gousiadou and
Skaltsa (2003)
Helal et al. (1997)
Sarg et al. (1988), Al-Easa et al. (1990)
Sakakibara et al. (1977), Cassady et al.
(1979), Jakupovic et al. (1986), Tešević et al.
(1998b), Gürbuz et al. (2006), Ozcelik et al.
(2009)
Nowak et al. (1986c, 1996),Nowak (1992)
Nowak et al. (1986a,c, 1996), Nowak (1992),
Öksük and Topçu (1994)
Nowak et al. (1986c), Nowak (1992), Nowak
et al. (1996)
Nowak et al. (1986b,a, 1996), Nowak (1992)
Nowak et al. (1986b, 1996), Nowak (1992)
Nowak et al. (1986b, 1996), Nowak (1992)
Nowak et al. (1986b,a, 1996), Nowak (1992)
Nowak et al. (1986b, 1996), Nowak (1992)
Nowak (1992), Nowak et al. (1996)
Nowak et al. (1986b, 1996), Nowak (1992)
Nowak et al. (1986b)
Nowak et al. (1986b,a, 1996), Nowak (1992)
Berdin et al. (1999)
Jiang et al. (1996)
Dai et al. (2001)
Fernandez et al. (1995)
OH
O
H
Name
chlorohyssopifolin A;
centaurepensin; hyrcanin
Centaurea adjarica
Centaurea aegyptiaca
Centaurea bella
O
O
O
Centaurea conifera (=Leuzea conifera)
Centaurea hyrcanica
Centaurea hyssopifolia
Centaurea imperialis
Centaurea linifolia
Centurea musimomum
Centaurea nigra
Centaurea scoparia
Centaurea sinaica
Centaurea solstitialis
Chartolepis bieberstenii
Chartolepis glastifolia
Chartolepis pterocaula
225
H
Cl
HO
HO
Cl
Psephellus carthalinicus
Psephellus colchicus
Psephellus daghestanicus
Psephellus dealbatus
Psephellus karabaghensis
Psephellus nogmovii
Psephellus somcheticus
Psephellus taochius
Psephellus zangezuri
Rhaponticum serratuloides
Rhaponticum uniflorum
Serratula strangulata
chlorohyssopifolin A 17-epi; 17- Centaurea conifera (=Leuzea conifera)
epi -centaurepensin
Centaurea musimomum
Centaurea solstitialis
Chartolepis glastifolia
OH
O
H
O
O
Medjroubi et al. (2005)
Tešević et al. (1998b)
Öksük and Topçu (1994)
O
226
227
H
OH
HO
HO
Cl
Serratula strangulata
Dai et al. (2001)
chlorohyssopifolin E
Centaurea aegyptiaca
Centaurea hyssopifolia
Centaurea linifolia
Sarg et al. (1987)
Gonzalez et al. (1974b, 1977a)
Gonzalez et al. (1977a, 1978b), Nowak et al.
(1986a)
Chlorohyssopifolin D
Centaurea hyssopifolia
Centaurea linifolia
Gonzalez et al. (1974b, 1977a)
Gonzalez et al. (1977a, 1978b), Nowak et al.
(1986a)
OH
O
H
17-O-(p-hydroxyphenylethanol)-centaurepensin
O
O
O
228
H
OH
HO
HO
Cl
OCH2CH3
O
H
O
O
O
229
deacetylcentaurepensin-8-O-(40 - Centaurea adjarica
hydroxy)-tiglate; cebellin D
Centaurea bella
H
HO
HO
Cl
O
OH
H
O
O
O
Centaurea imperialis
Centaurea marshalliana
Centaurea scoparia
Nowak et al. (1989a, 1996), Nowak (1992)
Nowak et al. (1986d, 1996), Nowak (1990,
1992, 1993a,b)
Rustaiyan et al. (1984)
Nowak et al. (1989a, 1996), Nowak (1992)
Youssef and Frahm (1994a), Helal et al.
(1997)
Please cite this article in press as: Bruno, M., et al. Sesquiterpenoids in subtribe Centaureinae (Cass.) Dumort (tribe Cardueae, Asteraceae): Distribution, 13C
NMR spectral data and biological properties. Phytochemistry (2013), http://dx.doi.org/10.1016/j.phytochem.2013.07.002
39
M. Bruno et al. / Phytochemistry xxx (2013) xxx–xxx
Table 9 (continued)
No
Structure
230
Name
Taxa
Ref.
Centaurea solstitialis
Chartolepis glastifolia
Chartolepis pterocaula
Centaurea scoparia
Nowak (1992), Nowak et al. (1996); Tešević
et al. (1998b)
Nowak et al. (1986c, 1996), Nowak (1992)
Nowak (1992), Nowak et al. (1996)
Youssef and Frahm (1994a)
Centaurea scoparia
Youssef (1998)
4b-(chloromethyl)-3b,4aCentaurea scoparia
dihydroxy-8a- (sarracenoyloxy)1aH,5aH,6bH,7aH-guai10(14),11(13)-dien-6,12-olide
Youssef (1998)
repensolide; cebellin E
chloroscoparin
H
HO
O
HO
Cl
OAc
H
O
O
O
231
H
HO
O
HO
Cl
CHO
H
O
O
4b-(chloromethyl)-3b,4adihydroxy-8a- (30 -formyl-20 methyl-propenoyloxy)1aH,5aH,6bH, 7aH-guai10(14),11(13)-dien-6,12-olide
O
232
H
OH
HO
O
HO
Cl
H
O
O
O
233
HO
H
HO
chlororepdiolide
Acroptilon repens
Jakupovic et al. (1986)
Nowak et al. (1989a, 1996), Nowak (1992)
Nowak et al. (1986d, 1996), Nowak (1990,
1992, 1993a,b)
Cis et al. (2006), Zhang et al. (2010)
Nowak et al. (1988, 1996), Nowak (1992),
Kokoska and Janovska (2009)
Stevens and Wong (1986)
diain
Centaurea scoparia
Youssef and Frahm (1994b)
15-deschloro-15-hydroxychlorohysssopifolin B
Amberboa ramosa
Khan et al. (2005a, 2010)
hermanoid 2; 15-deschloro-15hydroperoxychlorohysssopifolin B
Centaurea hermannii
Öksük et al. (1994)
pterocaulin; repdiolide triol
Centaurea incana
Chartolepis biebersteinii
Chartolepis glastifolia
Chartolepis pterocaula
Massiot et al. (1986)
Nowak et al. (1986c, 1996), Nowak (1992)
Öksük and Topçu (1994)
Nowak et al. (1986c, 1996), Nowak (1990,
1992)
Rhaserolide
Rhaponticum serratuloides
Berdin et al. (1999), Zhang et al. (2010)
O
HO
Cl
H
Rhaponticum pulchrum
Stemmamarca carthamoides
O
O
Acroptilon repens
Centaurea adjarica
Centaurea bella
O
234
HO
H
HO
HO
Cl
O
H
O
O
O
235
H
HO
HO
Cl
O
H
OH
O
O
O
236
H
HO
HO
HO
OH
H
O
O
237
H
HO
HO
HOO
OH
H
O
O
238
H
HO
HO
HO
O
H
O
O
O
239
H
HO
HO
AcO
O
H
O
O
O
(continued on next page)
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NMR spectral data and biological properties. Phytochemistry (2013), http://dx.doi.org/10.1016/j.phytochem.2013.07.002
40
M. Bruno et al. / Phytochemistry xxx (2013) xxx–xxx
Table 9 (continued)
No
Structure
240
H
HO
O
HO
HO
H
Name
Taxa
Ref.
15-deschloro-15hydroxychlorojanerin
Amberboa ramosa
Khan et al. (2005a, 2010)
Centaurea conifera (=Leuzea conifera)
Centaurea hololeuca
Centaurea scoparia
Rhaponticum pulchrum
Bruno et al. (1998)
Rosselli et al. (2006a)
Dawidar et al., 1989
Cis et al. (2006), Zhang et al. (2010)
Centaurea hermannii
Öksük et al. (1994)
Chartolepis glastifolia
Öksük and Topçu (1994)
15-deschloro-3b-acetyl-15hydroxy-chlorojanerin
Centaurea hermannii
Öksük et al. (1994)
cebellin G; 15-deschloro-15acetoxy-chlorojanerin
Centaurea adjarica
Centaurea bella
Nowak et al. (1986d)
Nowak et al. (1986d, 1996), Nowak (1990,
1992, 1993a,b)
Öksük et al. (1994)
Rosselli et al. (2006a)
Dawidar et al., 1989
Cis et al. (2006), Zhang et al. (2010)
OH
O
O
O
241
Hermanoid 1 15-deschloro-15hydroperoxy-chlorojanerin
H
HO
HO
HOO
O
H
OH
O
O
O
242
H
AcO
HO
HO
O
H
OH
O
O
O
243
H
HO
O
HO
AcO
H
OH
Centaurea hermannii
Centaurea hololeuca
Centaurea scoparia
Rhaponticum pulchrum
O
O
O
244
H
HO
O
HO
HO
H
babylin B
Centaurea babylonica
Bruno et al. (2005a)
Centaurea conifera (=Leuzea conifera) or Bruno et al. (1998)
245
Centaurea hololeuca
Rosselli et al. (2006a)
15-deschloro-15-hydroxyepisolstiolide
Chartolepis glastifolia
Öksük and Topçu (1994)
cebellin J; desacyllinochlorin C;
15-deacetylrhaposerin
Centaurea adjarica
Centaurea babylonica
Centaurea bella
Nowak et al. (1996)
Bruno et al. (2005a)
Nowak et al. (1986d, 1996), Nowak (1990,
1992, 1993a,b)
Rosselli et al. (2006a)
Gonzalez et al. (1977a), Nowak et al. (1986a)
Öksük and Topçu (1994)
Berdin et al. (2001), Zhang et al. (2010)
Gonzalez et al. (1977a, 1978b), Nowak et al.
(1986a)
O
O
O
O
245
H
HO
O
O
HO
HO
H
O
O
O
246
H
Cl
HO
OH
O
HO
HO
H
linochlorin C
Centaurea hololeuca
Centaurea linifolia
Chartolepis glastifolia
Rhaponticum serratuloides
Centaurea linifolia
rhaposerin
Rhaponticum serratuloides
Berdin et al. (1999), Zhang et al. (2010)
Epicebellin J
Chartolepis glastifolia
Ö ksü k and Topç u (1994)
O
O
O
247
H
Cl
AcO
HO
HO
OH
O
H
O
O
O
248
H
Cl
HO
HO
AcO
OH
O
H
O
O
O
249
H
Cl
HO
HO
HO
OH
O
H
O
O
O
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NMR spectral data and biological properties. Phytochemistry (2013), http://dx.doi.org/10.1016/j.phytochem.2013.07.002
41
M. Bruno et al. / Phytochemistry xxx (2013) xxx–xxx
Table 9 (continued)
No
Structure
250
H
OH
HO
HO
H
Taxa
Ref.
Sinicin A
Centaurea pseudosinaica
Amer et al. (2001)
Sinicin B
Centaurea pseudosinaica
Amer et al. (2001)
13-deschloro-15-hydroxy-8desacylcentaurepensin-8-O-(40 hydroxy)- tiglate
Centaurea imperialis
Rustaiyan et al. (1984)
Cebellin H
Centaurea bella
Nowak et al. (1986d, 1996), Nowak (1990,
1992, 1993a,b)
19-desoxypicrolide A
Chartolepis glastifolia
Öksük and Topçu (1994)
Picrolide A
Acroptilon repens
Stevens et al. (1991)
Hololeucin
Centaurea hololeuca
Rosselli et al. (2006b)
Rhaserin
Rhaponticum serratuloides
Berdin et al. (2001), Zhang et al. (2010)
3-oxo-4a-hydroxy-15-hydroxy1aH,5aH, 6bH,7aH,11bH-guai10(14)-ene-6,12-olide
Centaurea musimomum
Medjroubi et al. (1997)
3-oxo-4a-acetoxy-15-hydroxy1aH,5aH, 6bH,7aH,11bH-guai10(14)-ene-6,12-olide
Centaurea musimomum
Medjroubi et al. (1997)
OH
O
HO
Name
O
O
O
251
H
OH
HO
OH
O
HO
H
HO
O
O
O
252
H
HO
O
OH
HO
H
HO
O
O
O
253
H
HO
O
OH
HO
H
AcO
O
O
O
254
H
HO
O
HO
O
H
O
O
O
O
HO
255
H
HO
O
HO
O
H
O
OH
O
O
O
HO
256
H
O
O
H
O
O
O
O
HO
OH
O
257
HO
H
HO
HO
HO
O
H
O
O
O
258
H
O
HO
HO
H
O
O
259
H
O
AcO
HO
H
O
O
13
(continued
on next page)
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Distribution,
C
NMR spectral data and biological properties. Phytochemistry (2013), http://dx.doi.org/10.1016/j.phytochem.2013.07.002
42
M. Bruno et al. / Phytochemistry xxx (2013) xxx–xxx
Table 9 (continued)
No
Structure
260
H
HO
Name
Taxa
Ref.
Saussureolide
Amberboa ramosa
Khan et al. (2005b, 2010)
ramosine; 15-dechloro-15hydroxychlorojanerin
Amberboa ramosa
Khan et al. (2004b, 2010)
ludartin
Amberboa ramosa
Khan et al. (2004c)
Grosheiminol
Grossheimia macrocephala
Daniewski et al. (1982), Barbetti et al. (1985)
Grosshemin; grosheimin
Amberboa lippii
Gonzalez et al. (1967), Gonzalez et al., 1970,
Gonzalez et al., 1977a, Gonzalez et al., 1978a,
Breton et al. (1968), Bermejo et al. (1969),
Rybalko et al. (1975), Khan et al. (2010)
Rustaiyan et al. (1981a), Öksüz et al. (1982),
Nowak et al. (1986a), Gürkan et al. (1998)
Yayli et al. (2006)
Gonzalez et al. (1977a)
Adekenov et al. (1986b), Adekenov (1995)
Krasnov et al. (2006), Kaminskii et al.
(2010b,c)
Nowak et al. (1986a)
Mukhametzhanov et al. (1969d), Rybalko
et al. (1975), Nowak et al. (1986a,c, 1996),
Adekenov et al. (1986b, 1991), Nowak
(1992), Adekenov (1995)
Nowak et al. (1986c, 1996), Nowak (1990,
1992)
Rybalko et al. (1964), Rybalko et al., 1975,
Rybalko and Sheichenko (1965), Sheichenko
and Rybalko (1970, 1972), Bialecki et al.
(1973), Gonzalez et al. (1977a, 1978a),
Daniewski et al. (1982), Barbetti et al. (1985),
Nowak et al. (1986a), Monea (1986),
Piacentini et al. (1986, 1987), Adekenov
(1995)
Bialecki et al. (1973), Popova et al. (1974)
Gonzalez et al. (1973b, 1977a), Nowak et al.
(1986a), Khan et al. (2010)
OH
HO
H
HO
O
O
261
H
HO
O
HO
OH
H
HO
O
O
O
262
O
H
O
O
263
H
HO
OH
H
O
O
264
H
O
OH
H
Centaurea behen
O
Centaurea
Centaurea
Centaurea
Centaurea
O
helenioides
ornata
ruthenica
scabiosa
Chartolepis glastifolia
Chartolepis intermedia
Chartolepis pterocaula
Grossheimia macrocephala
265
Muricatin
H
HO
O
H
Grossheimia ossica
Amberboa muricata
OH
O
O
O
266
H
grosheimin-20 S,30 -dihydroxyisobutyrate
OH
O
OH
O
H
Centaurea ornata
Navarro et al. (1990)a, Bastos et al. (1994)
O
O
O
H
HO
267
HO
O
H
OH
O
O
a
Stereochemistry of the side
chain not assigned in the original
paper.
Acrorepiolide
Acroptilon repens
Rustaiyan et al. (1981b), Rustaiyan and
Nazarians (1984)
O
Please cite this article in press as: Bruno, M., et al. Sesquiterpenoids in subtribe Centaureinae (Cass.) Dumort (tribe Cardueae, Asteraceae): Distribution, 13C
NMR spectral data and biological properties. Phytochemistry (2013), http://dx.doi.org/10.1016/j.phytochem.2013.07.002
43
M. Bruno et al. / Phytochemistry xxx (2013) xxx–xxx
Table 9 (continued)
No
Structure
268
H
O
O
H
HOH2C
OH
Name
Taxa
Ref.
15-hydroxy-8-(40 hydroxymethacroyloxy)10(14),11(13)-guaiadien-6,12olide
Centaurea tweediei
Fortuna et al. (2001)
Isolipidiol
Amberboa lippii
Gonzalez et al. (1970, 1977a), Rybalko et al.
(1975), Khan et al. (2010)
Gonzalez et al. (1973b, 1977a), Nowak et al.
(1986a), Khan et al. (2010)
Gonzalez Collado et al. (1986a)
Daniewski et al. (1982), Nowak et al. (1986a)
O
O
O
269
H
HO
Amberboa muricata
OH
H
Centaurea clementei
Grossheimia macrocephala
O
O
270
H
tetrahydro-dehydrozaluzanin C; Centaurea webbiana
dihydroestafiatone
Gonzalez et al. (1972b, 1977a, 1978a)
8a,9a-dihydroxy-4b,15,11b,13tetrahydro-dehydrozaluzanin C
Amberboa tubuliflora
Ahmed et al. (1990), Khan et al. (2010)
Amberbin A;
dihydrocumambrin A
Amberboa ramosa
Ibrahim et al. (2010)
Amberbin B
Amberboa ramosa
Ibrahim et al. (2010)
Lipidiol
Amberboa lippii
Gonzalez et al. (1970, 1977a, 1978a), Rybalko
et al. (1975), Khan et al. (2010)
Amberboin
Amberboa lippii
Centaurea sinaica
Gonzalez et al. (1967), Gonzalez et al., 1970,
Gonzalez et al., 1977a, Gonzalez et al., 1978a,
Bermejo et al. (1969), Rybalko et al. (1975),
Khan et al. (2010)
Al-Easa et al. (1990)
cynaratriol
Centaurea musimomum
Lopes-Rodriguez et al. (2009)
4b,15-dihydro-3-dehydro-13acetylsolstitialin A
Centaurea behen
Centaurea musimomum
Centaurea solstitialis ssp. shouwii
Öksüz et al. (1982, 1993)
Nowak, 1990, Medjroubi et al. (2005)
Bruno et al. (1991b), Ö ksü z et al. (1993)
O
H
O
O
271
OH
H
O
OH
H
O
O
272
OH
H
OAc
H
O
O
273
O-β-D-glucose
H
OAc
H
O
O
274
H
HO
OH
H
O
O
275
H
O
OH
H
O
O
276
H
HO
OH
H
O
OH
O
277
H
O
OAc
H
O
OH
O
(continued on next page)
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NMR spectral data and biological properties. Phytochemistry (2013), http://dx.doi.org/10.1016/j.phytochem.2013.07.002
44
M. Bruno et al. / Phytochemistry xxx (2013) xxx–xxx
Table 9 (continued)
No
Structure
278
H
Name
Taxa
Ref.
4b,15-dihydro-3dehydrosolstitialin A
Centaurea behen
Centaurea musimomum
Centaurea ptosimopappa
Rustaiyan et al. (1981a)
Gonzalez-Platas et al. (1999), Medjroubi et al.
(2003b)
Çelik et al. (2006)
Clementein C
Centaurea clementei
Gonzalez Collado et al. (1986b,a)
Pseudoivalin
Serratula latifolia
Rustaiyan and Feramarzi (1988)
4a-hydroxy-10bhydroperoxyguaia-1,11(13)dien-12, 8b-olide
Serratula latifolia
Rustaiyan and Feramarzi (1988)
4a-hydroxy-10ahydroperoxyguaia-1,11(13)dien-12, 8b-olide
Serratula latifolia
Rustaiyan and Feramarzi (1988)
4a-hydroxy-1bhydroperoxyguaia10(14),11(13)-dien-12, 8b-olide
Serratula latifolia
Rustaiyan and Feramarzi (1988)
(3a,3aR,4S,6aR,9aS,9bR)-4hydroxy-3-methyl-6methyleneoctahydroazuleno[4,5-b]furan-2,8(3H,9bH)dione
Centaurea deflexa
Chicca et al. (2011)
O
OH
H
O
OH
O
279
O
H
HO
OH
O
H
O
O
O
280
O
H
OH
O
281
OOH
O
H
OH
O
282
OOH
O
H
OH
283
O
HOO
O
H
OH
284
O
H
O
OH
H
O
O
against six bacteria and eight fungal species. All compounds
showed greater antibacterial and antifungal activities than the positive control used, streptomicyn and miconazole, respectively
(Djeddi et al., 2007, 2008b). On the other hand compounds 34
and 35, epoxygermacranes isolated from Stizolophus balsamita,
exhibited only moderate antimicrobial activity against three bacterial strains and antifungal activity toward Candida candicans (Suleimenov et al., 2005a), and 8-hydroxyzaluzanin C (149) against S.
aureus, and E. coli (Ndom et al., 2006). Antimicrobial properties
against S. aureus and Micrococcus luteus were determined, by disc
diffusion method, for compounds 142 and 143, structurally similar
to 149 (Negrete et al., 1984).
Santamarin (99), alantolactone (121), pseudoivalin (280), 9ahydroxypartenolide (28) and grosshemin (264) were shown to
have antibiotic activity against five bacteria, the best compound
being 9a-hydroxypartenolide (28) (Picman, 1983a). This germacrane at concentrations of 50 and 100 lg/disc, inhibited the growth of
several microorganism showing the most relevant antibacterial
activity against E. coli (El Hassany et al., 2004).
In radio-respirometric bioassays against Mycobacterium tuberculosis and Mycobacterium avium, dehydrocostus lactone (142)
exhibited MIC of 2 and 16 lg/mL, respectively (Cantrell et al.,
1998), whereas costunolide (1), santamarine (99), reynosin (100)
(Fischer et al., 1998) and alantolactone (121) (Cantrell et al.,
1999) are moderately active against M. tuberculosis with MIC
around 32–64 lg/mL.
Costunolide (1) and dehydrocostus lactone (142), were the
compounds responsible for the antimycobacterial activity against
M. tuberculosis H37Rv with MICs of 6.3 and 12.5 mg/L, respectively.
Antimycobacterial activity against drug-resistant (rifampicinresistant) M. tuberculosis clinic isolates appeared to be better for
the mixture than for pure compounds because of a synergistic effect (Luna-Herrera et al., 2007). Costunolide (1), isolated from
Chrysanthemum boreale, also showed antibacterial activity against
Vibrio parahaemolyticus, B. subtilis, B. cereus and S. aureus (Jang
et al., 1998a).
The antibacterial activity of costunolide (1) against six plant
pathogenic bacteria, Pseudomonas solanacearum, Sarcina lutea,
Agrobacterium tumefaciens, Erwinia amylovolora, Erwinia cartovora
and Corynebacterium fascians, was also evaluated using the agar
dilution method. Costunolide was as effective as streptomycin
against C. fascians with a MIC value of 10 mg/L (Abdelgaleil and
Ahmed, 2005).
Anti-Helicobacter pylori effect of costunolide (1) was also investigated using one commercial strain (H. pylori ATCC 43504) and
three clinical strains (H. pylori 4, 43, 82548). Costunolide exhibited
Please cite this article in press as: Bruno, M., et al. Sesquiterpenoids in subtribe Centaureinae (Cass.) Dumort (tribe Cardueae, Asteraceae): Distribution, 13C
NMR spectral data and biological properties. Phytochemistry (2013), http://dx.doi.org/10.1016/j.phytochem.2013.07.002
C
142a;p
1
142a2
143a3
147a3
148a4
149a5
149b6
150a7
152a8
153a9
154a10
155a9
156a9
158a7
160a7
161a8
162a5
164a11
165a12
166n:r:
13
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
10
20
30
40
100
200
47.3
30.7
32.4
151.0
51.7
85.0
44.8
30.4
36.0
148.9
139.4
169.9
119.7
112.3
109.2
47.6
30.3
32.6
151.2
52.0
85.2
45.1
30.9
36.3
149.2
139.7
170.2j
120.2j
112.6k
109.6k
49.3
30.3
32.0
150.0
53.1
78.6
51.0
72.2
42.7
143.7
138.1
169.9
123.3
116.1
111.1
44.0
38.9
73.3
152.9
49.8
83.9
45.4
30.4
34.0
147.9
139.6
170.0
120.1
114.3
111.0
44.6
36.5
74.7
148.0
50.3
83.3
45.3
30.6
34.5
147.7
139.5
170.0
120.4
114.4
113.6
170.8
21.3
45.2
39.2
73.7
152.4
51.3
79.0
51.0
71.9
41.3
142.7
138.1
169.9
123.2
117.1
113.2
46.0
40.0
73.1
154.3
51.9
80.9
51.7
74.1
42.9
144.7
140.6
172.0
122.9
117.0
112.1
45.6
36.5
74.7
147.3
51.7
78.1
51.1
72.0
41.4
142.3
138.0
169.5
123.2
117.5
115.8
170.7
21.3
45.1
34.4
71.8
146.7j
52.0
76.6
50.5
74.3
36.3
58.4
138.3j
170.7
123.2
55.7
116.6
169.3
21.2
48.8⁄
38.1
73.6
152.0
48.3⁄
78.8
40.9
75.2
81.0
143.8
136.3
170.0
125.1
113.6
111.9
169.6
21.1
44.8
33.8
75.6
149.9
50.0
85.0
46.0
24.0
37.8
74.9
139.2
169.3
120.0
53.1
114.5
169.3
21.2
48.8⁄
36.0
74.5
147.4
47.8⁄
78.8
41.1
75.2
81.0
143.7
135.9
170.6
125.5
113.8
113.1
170.6
21.1
48.7⁄
36.1
74.6
146.9
47.0⁄
79.4
40.9
77.6
79.7
147.7
136.1
171.1
125.3
112.5
112.4
170.4
20.9
45.4
39.0
73.7
152.3
51.4
78.7
47.7
73.9
37.0
141.9
137.7
169.6
122.2
117.9
113.2
176.4
34.2
18.9
18.6
45.3
39.1
73.8
152.4
51.4
78.6
47.7
74.1
37.2
141.9
137.5
169.2
122.6
118.1
113.5
166.4
136.1
126.6
18.3
45.3
39.1j
73.8
152.2k
51.4
78.3l
47.7
75.2l
36.9j
141.3k
137.4k
169.8
122.3
118.8
113.7
168.8
53.8
52.8
17.4
45.3
39.1
73.7
152.2
51.4
78.6
47.6
74.3
37.0
141.8
137.4
169.2
122.7
118.2
113.5
165.4
139.4
126.6
62.1
45.6j
39.1
73.7
152.0
51.7j
78.1
47.3
75.9
35.8
141.4
137.5
168.8
122.1
118.7
114.1
171.7
74.7
51.1
23.4
45.3
39.0
73.5
152.1
51.4
78.6
47.2
73.9
36.5
141.9
137.3
169.6
123.0
118.1
113.6
171.1
42.4
64.4
13.5
45.3
38.3
73.2
151.8
51.5
78.1
46.9
75.2
35.6
141.6
136.8
169.5
123.6
118.1
113.8
174.8
76.0
68.1
21.6
C
168a14
169a14
171a14
176a;p
16
176i16
180a17
181e18
181i16
182e18
183a18
184e19
186e20
188a21
189d21
190a5
191a7
192a3
193a3
194a3
195n:r:
13
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
10
20
30
40
50
100
200
300
400
500
45.3
39.1
73.7
152.3
51.3
78.4n
47.8
73.8
37.2
141.9
137.4
169.2
122.6
118.0
113.5
166.9
128.3
136.6
14.6
12.0
45.1
38.9
73.6
152.1
51.2
78.6
47.5
74.1
36.9
141.7
137.3
169.2
122.7
118.1
113.4
166.2
127.7
141.9
59.7
12.7
45.5
36.3
75.0
152.2
51.4
77.4n
47.7
74.1
37.5
141.6
137.2
169.1
122.9
118.4
116.0
167.2
128.4
141.3
59.9
12.8
166.4
128.0
140.6
59.8
12.8
51.4
77.3
78.9
147.2
46.5
78.8
47.9
73.8
35.8
139.4
137.2
169.1
n.r.
n.r.
n.r.
166.5
135.9
n.r.
n.r.
46.8
78.9
79.8
151.3
52.9
78.5
48.4
74.5
36.8
141.5
138.9
169.2
121.3
119.2
111.9
166.5
136.7
124.6
18.3
47.3
30.1
32.3
149.6
52.1
85.0
47.5
25.2
36.0
132.0
77.2
180.0
64.6
112.4j
109.8j
42.8
38.0
72.7
152.3
52.2
82.1
49.9
26.2
35.6
148.7
n.r.
179.0
62.9
113.1
110.4
43.5
39.4
73.2
155.4
53.4
83.2
50.7
27.7
37.6
150.5
78.6
180.5
64.9
112.9
108.7
44.1
36.6
75.4
149.1
52.4
82.8
51.1
26.7
36.3
148.6
n.r.
179.7
63.5
113.6
113.6
42.9
38.3
73.3
154.6
52.5
82.0
49.6
26.9
35.9
148.6
75.5
176.5
64.1
113.6
111.3
44.5*
30.5
30.2
151.6
53.3
79.7
55.5
68.0
32.3
145.1
76.5
178.9
44.1*
115.0
110.4
44.9
39.1
73.3
153.5
51.7
79.0
51.0
70.3
30.0
143.0
75.5
178.1
43.1
117.1
112.5
165.5
140.9
125.0
61.1
47.2
30.1j
32.3j
151.1
52.5
80.2
55.4
75.1
47.0
144.5
41.6
179.1
16.1
114.3k
109.7k
43.6
41.3
75.0
155.7
50.4
80.3
55.7
73.7
48.4
145.8
39.8
178.5
15.4
113.4j
110.9j
44.2
39.0
73.6
153.0
50.7
79.1
56.0
74.9
44.8
143.2
42.0
178.6
15.9
116.2
112.0
44.3
38.9
73.6
152.8
50.7
79.0
53.2
75.7
40.5
142.3
41.3
177.8
15.6
117.2
112.4
176.2
34.2
19.1
18.7
44.3
38.8
73.6
152.7
50.7
78.9
53.1
76.1
40.3
142.1
41.4
177.8
15.5
117.4
112.5
174.9
42.1
64.4
13.5
44.0
38.6
73.4
152.6
50.3
78.9
53.2
76.0
40.3
142.1
41.2
177.8
15.4
117.1
112.1
166.3
135.9
126.4
18.2
44.1
38.6
73.5
152.5
50.4
78.8
53.3
76.2
40.3
142.0
41.2
177.7
15.4
117.3
112.4
165.2
139.1
126.4
62.1
44.5
38.7
73.3
152.4
51.0
78.7
52.2
77.7
39.0
141.8
41.3
178.4
15.2
117.5
112.8
175.0
75.9
68.0
21.8
66.4
24.7
64.3
24.1
C
196a;o
22
199a24
201a25
208i27
209a28
210a28
211a29
212i27
213a14
214i16
215g30
217b31
45.8
38.8
75.2
69.1
45.6
37.5
75.0
68.3
45.4
37.4
75.7
68.2
46.2
38.0j
76.5
68.2
46.1
38.9
75.3
69.1
45.6
37.5
76.1
68.2
47.2
78.3
79.5
66.6
49.2
73.1
77.2
65.4
48.9
40.0
77.1
85.8
1
2
3
4
169.9
21.0
44.6
36.6
74.9
148.2
198a23
48.4
29.7
33.6
150.3
43.6
38.6
73.7
152.7
43.7
38.6
73.7
152.6
202a25
43.8
38.6
73.8
152.5
203e25
44.4
46.6
75.6
150.1
204a25
44.3
46.7
75.9
150.3
205d26
44.0
38.9
73.0
154.3
206a14
45.2
37.3
75.0
68.4
207a7
208a7
j
j
45.7
37.7
76.1
68.3
45.7
37.7
76.1
68.2
⁄
M. Bruno et al. / Phytochemistry xxx (2013) xxx–xxx
45
Please cite this article in press as: Bruno, M., et al. Sesquiterpenoids in subtribe Centaureinae (Cass.) Dumort (tribe Cardueae, Asteraceae): Distribution, 13C
NMR spectral data and biological properties. Phytochemistry (2013), http://dx.doi.org/10.1016/j.phytochem.2013.07.002
Table 10
C NMR data of guaianes.
13
46
C
196a;o
22
198a23
199a24
201a25
202a25
203e25
204a25
205d26
206a14
207a7
208a7
208i27
209a28
210a28
211a29
212i27
213a14
214i16
215g30
217b31
5
6
7
8
9
10
11
12
13
14
15
10
20
30
40
50
60
51.1
79.2
54.1
85.3
42.8
142.8
41.9
178.3
16.3
117.1
114.5
101.5
72.1
73.3
68.6
72.1
62.1
52.9
79.4
50.7
70.0
36.2
144.4
42.6
178.2
16.1
116.0
110.7
49.9
78.9
53.4
69.9
45.0
143.1
38.1
179.1
11.2
115.9
112.6
49.8
79.0
50.7
72.0
40.4
142.2
38.1
178.3
11.3
117.0
112.7
166.4
136.2
126.1
18.2
49.9
78.8
50.7
72.2
40.3
142.3
38.1
177.3
11.3
117.3
113.1
166.8
144.3
126.3
62.3
50.2
79.1
53.6
70.8
36.5
142.2
39.1
179.2
11.2
115.0
113.6
165.8
145.4
123.2
61.3
50.6
79.5
53.5
70.4
36.5
145.4
39.1
179.2
11.2
115.0
113.5
167.2
137.6
126.2
18.4
49.7
79.3
57.6
73.3
42.7
145.0
46.5
175.8
56.5
110.3
114.9
53.7
23.6
23.6
53.7
52.4
77.4
51.1
71.5
40.8
142.2
137.8
170.3
123.1
117.3
48.4
53.1
77.0
47.9j
74.0
36.5
141.6
137.2
169.2
122.6
118.4
48.5
166.5
136.0
126.7
18.2
53.1
76.8
47.9j
74.2
36.5
141.4
137.0
169.0
122.7
118.6
48.5
165.3
139.3
126.7
62.2
52.8
77.5
47.8
74.3
36.8
142.2
138.6
169.0
121.4
117.7
48.5
165.7
143.1
127.7
60.9
53.0
76.7
47.9
76.0
36.1
140.9
137.0
168.9
122.3
118.8
48.5
169.9
53.8
52.8
17.3
52.7
76.6
47.6
75.1
36.5
141.3
136.4
169.2
123.5
118.6
48.4
170.1
53.7
52.9
17.2
53.7
76.6
47.5
75.8
35.3j
140.9
137.3
168.7
122.2
119.3
48.5
175.0
75.8
68.5
21.6
53.2
77.3
47.6
75.2
36.1
142.8
138.5
169.0
121.3
118.0
48.9
173.3
75.3
52.1
24.2
52.9
76.9
48.0
74.0
36.5
141.3
137.0
169.1
122.7
118.6
48.5
166.5
127.9
141.7
59.8
12.7
53.1
78.0
49.4
74.4
37.0
141.0
138.4
169.0
121.4
119.4
47.8
165.5
136.6
126.5
18.3
47.1
77.4
51.7
78.9
36.7
135.2
136.9
168.4
121.9
119.4
47.3
166.5
128.1
138.2
11.9
14.4
59.8
79.0
50.6
72.5
40.0
145.2
140.3
171.6
122.6
116.9
50.1
C
218a7
219a7
219b23
219i32
220b33
221b33
222a38
223a28
224a28
224i27
225a28
226d34
229h31
230b31
231b35
232b35
234i36
235b6
236b23
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
10
20
30
40
50
100
200
300
400
500
600
700
800
47.1
37.8
77.3
84.5
57.6
76.4
46.6
73.9
35.2
142.3
137.0
168.8
122.7
117.9
49.9
166.5
136.0
126.6
18.2
47.1
37.8
77.2
84.5
57.5
76.3
46.5
74.1
35.2
142.2
136.8
168.7
122.8
117.9
49.8
166.4
139.3
126.8
62.3
48.9
39.6
77.0
85.5
59.1
78.7
47.9
75.6
36.1
144.4
139.2
171.0
122.3
117.4
50.2
166.5
141.5
126.2
61.6
46.6
40.3
76.5
85.4
59.6
77.6
48.7
74.5
35.4
144.8
139.0
169.2
121.1
116.9
51.3
165.9
142.4
124.9
61.1
50.0
40.1
77.0
85.9
59.4
78.4
47.7
75.4
35.9
144.9
139.9
170.9
122.4
117.7
50.2
174.5
42.2
63.9
14.9
50.0
40.0
77.1
85.9
59.5
78.5
47.5
75.5
35.9
144.9
139.9
170.9
122.5
117.7
50.2
169.7
45.9
180.2
15.2
46.4
37.7
77.2
84.5
57.5
77.2
47.1
75.0
34.8
141.6
136.8
168.5
122.5
118.3
49.9
169.9
53.8
52.8
17.4
46.2
37.6
76.0
84.4
57.4
77.2
46.9
75.0
35.1
142.1
136.2
168.7
123.7
118.0
49.8
170.1
53.7
52.9
17.3
46.4
37.9
76.0
84.6
57.5
77.2
47.3
75.9
34.6
141.8
136.9
168.3
122.4
118.5
50.0
173.1
74.7
51.2
23.4
48.6
40.3
76.3
85.3
59.4
77.5
46.5
75.4
35.1
144.6
138.9
169.0
121.1
117.1
51.2
173.5
75.2
52.2
24.3
46.6
38.0
76.1
84.7
57.5
77.4
47.1
76.0
34.7
142.0
136.4
168.3
123.3
118.3
50.0
173.0
75.1
50.9
23.9
48.6
40.0
76.6
85.2
59.2
77.3
46.9
76.1
35.2
144.6
139.0
169.4
121.5
117.5
50.4
173.9
79.3
51.8
24.0
47.6
39.1
76.1
84.4
58.5
77.1
46.4
74.1
35.1
143.9
138.0
169.0
121.6
116.8
50.1
166.8
126.9
143.7
59.2
12.5
49.0
40.0
77.0
85.8
59.8
78.5
47.6
75.6
35.9
145.1
139.5
170.8
122.1
117.5
50.1
168.2
128.9
143.5
59.7
12.6
176.4
22.1
47.8
39.7
76.2
84.6
58.3
77.2
46.5
74.3
35.0
143.8
138.2
169.7
122.3
116.5
50.0
166.6
130.2
132.7
193.1
13.2
48.3
40.2
77.0
85.2
59.2
77.3
46.9
75.0
35.6
145.0
139.3
170.8
122.1
117.2
50.1
167.4
132.1
141.9
14.3
55.7
58.4
83.3
84.1
83.9
60.1
77.6
47.2
74.4
36.7
142.8
138.8
169.0
120.9
118.0
50.9
166.5
136.7
126.3
18.3
48.6
39.9
77.0
85.9
60.0
78.5
49.9
76.8
36.7
145.2
44.7
180.1
40.1
116.7
49.9
166.4
142.1
125.3
61.5
48.3
37.8
77.9
85.8
55.5
79.4
51.6
70.7
36.8
144.7
139.5
173.2
122.7
116.3
64.5
C
238a7
239i27
240b23
241a37
24337
244a29
246a38
246i39
24827
249a38
254a38
255d32
255i32
256d40
257i39
258a41
259a41
260a;q
11
261b42
262a43
1
2
3
4
5
6
43.6
38.6
77.4
83.5
54.9
77.3
47.5
40.0
77.1
84.2
58.3
77.5
48.1
38.0
77.2
85.5
56.5
79.0
43.6
38.5
75.9
83.5
58.1
78.3
43.5
37.2
76.2
83.9
56.7
74.0
43.9
38.0j
77.0
83.5
55.3
78.0
44.1
38.1⁄
77.9
84.5
56.1
77.5
47.1
39.8
77.1
85.8
57.7
77.9
47.6
40.4
77.0
84.3
58.3
77.5
44.2
38.1⁄
77.9
84.5
56.1
77.5
47.9
38.4
77.1
83.9
57.9
77.6
47.6
39.5
77.0
84.7
58.3
77.5
46.6
40.1
77.1
84.7
58.6
77.7
47.1
37.9
85.1
95.7
52.7
77.3
52.5
78.4
84.5
81.0
54.8
77.7
39.6
43.9
219.7
77.2
51.4
87.2
39.7
43.9
219.0
75.6
51.4
86.9
41.5
32.8
78.2
81.4
55.0
76.9
48.3
37.5
77.9
85.8
55.5
79.4
133.9⁄
33.6
63.8
67.1
52.5
80.7
71.5
36.4
131.0
116.2
130.9
156.2
130.9
116.2
a=d
⁄
M. Bruno et al. / Phytochemistry xxx (2013) xxx–xxx
Please cite this article in press as: Bruno, M., et al. Sesquiterpenoids in subtribe Centaureinae (Cass.) Dumort (tribe Cardueae, Asteraceae): Distribution, 13C
NMR spectral data and biological properties. Phytochemistry (2013), http://dx.doi.org/10.1016/j.phytochem.2013.07.002
Table 10 (continued)
26.6
23.7
21.9
47.7
74.1
36.4
141.8
136.7
169.7
123.2
117.2
63.5
166.3
136.0
126.5
18.2
46.7
74.6
35.8
144.6
139.1
169.2
120.7
116.6
67.5
166.5
136.8
126.3
18.3
171.1
20.9
50.6
75.7
36.4
144.5
139.1
172.7
122.4
116.2
64.4
165.7
141.0
125.1
61.8
46.5
74.3
37.6
142.1
134.8
168.0
122.4
117.5
63.1
162.2?
136.3
126.6
62.4
46.1
76.4
35.3
142.0
139.2
172.0
121.4
116.5
65.7
165.0
135.6
124.8
60.7
165.0
20.2
47.5
75.2
36.9j
141.3
136.6
168.9
123.2
117.7
63.8
169.8
53.9
52.8
14.4
47.6
76.2
37.8⁄
141.8
136.8
169.7
123.5
118.4
63.8
173.5
75.1
51.7
23.4
47.0
75.6
36.2
144.6
138.9
169.4
121.1
116.7
63.9
173.5
75.4
52.2
23.3
46.8
75.4
35.5
144.5
138.9
169.1
121.0
117.0
67.5
173.4
75.4
52.2
24.3
171.1
20.9
47.7
76.5
37.8⁄
141.8
137.1
169.9
124.2
118.5
63.8
173.5
75.4
51.8
23.8
46.0
74.1
35.8
143.7
139.1
169.2
124.5
115.6
66.9
165.6
142.2
126.1
27.1
167.5
123.7
132.1
115.1
162.3
115.1
132.1
46.9
74.7
35.8
144.8
139.2
169.3
121.2
117.0
67.3
165.8
141.9
124.7
61.0
167.1
122.4
132.7
115.7
162.6
115.7
132.7
47.7
74.5
35.7
144.8
139.1
169.3
120.9
116.9
67.6
165.9
142.4
124.7
61.0
167.2
122.1
132.6
115.9
163.4
115.9
132.6
47.5
75.5
44.5
144.7
138.5
169.9
124.4
118.0
65.4
166.1
142.6
125.6
61.9
153.4
47.8
74.5
39.6
141.4
138.2
169.3
121.0
116.8
63.6
166.0
136.3
124.0
17.9
49.3
26.9
38.6
149.0
47.1
178.9
13.9
112.5
63.1
C
263i11
264a44
265e20
266a45
269b46
270a47
271a48
272a50
272b50
273b50
276a;q
51
277a52
278a52
279e20
284a53
287a54
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
10
20
30
40
50
60
100
200
43.3
38.5
87.4
44.9
51.4
81.6
49.9
67.8
41.6
143.5
136.3
169.3
121.2
116.8
18.3
40.1
43.2
219.1
46.9
51.0
82.3
49.1
73.1
47.9
143.1
136.3
169.9
125.8
115.6
14.9
43.4
40.7
78.1
46.7
51.7
81.9
50.4
75.2
n.r.
142.2
137.8
170.5
123.0
116.9
18.4
165.5
140.2
126.0
61.1
40.7
42.3
218.2
46.7
51.5
80.6
46.5
75.9
40.7
141.5
135.6
168.9j
125.2
117.3
15.1
174.7j
75.5
67.9
21.9
43.6
35.5
79.1
48.2
52.3
83.9
60.0
77.1
48.9
146.3
43.5
181.9
16.8
115.1
18.8
39.7
44.0
219.2
47.2
50.9
88.5
48.6
32.9
39.0
149.1
41.7
178.2
13.3
112.5
14.0
38.4
43.1
219.3
30.5
50.9
77.4
44.4
72.3
83.2
147.5
47.5
179.5
11.1
114.9
14.3
53.5
33.6
125.6
143.4
54.5
80.5
51.2
74.3
41.7
73.3
41.9
178.1j
15.3
31.5
17.5
55.5
34.0
127.1
143.8
52.7
82.1
54.4
75.5
44.2
73.4
46.6
180.8j
15.8
29.5
17.4k
42.6
36.8⁄
84.4
43.6
50.8
79.9
48.6
27.5
35.3⁄
148.7
79.7
171.7
62.7
113.1
18.0
39.5
43.7
219.1
47.1
51.2
86.8
49.5
27.1
38.3
148.7
75.5
176.2
64.0
112.7
14.0
169.2
20.5
39.6
43.9
219.7
47.1
51.4
87.2
49.4
26.9
38.6
148.9
77.2
178.8
63.1
112.5
13.9
42.9
41.3
78.2
47.1
54.6
81.4
51.2
71.9
38.5
142.8
75.9
178.2
43.2
115.9
18.6
165.5
140.9
125.0
61.1
40.3
44.1
219.0
44.1
52.2
82.9
55.6
70.5
49.2
143.5
47.9
175.9
15.2
116.3
22.9
23.3
43.6
208.5
34.3
30.7
37.8
75.6
37.3
17.2
139.0
170.4
122.5
18.2
30.0
170.1j
21.3
172.1j
21.2k
53.0
34.0
126.8
144.0
55.0
82.3
52.3
75.4
42.8
81.1
42.1
181.0j
15.7
26.1
17.7
98.4
78.2
71.8
75.5
77.7
62.9
172.1j
21.3
49.6
27.2
38.5
148.8
47.2
176.2
14.1
112.9
64.1
170.4
20.7
53.7
75.4
42.0
140.5
40.5
176.8
15.7
117.2
64.1
57.6
75.7
36.8
144.7
43.1
180.5
16.1
116.1
64.3
165.3
141.9
125.9
62.4
54.5
25.8
34.0
134.9⁄
139.4
169.5
117.8
22.7
19.0
M. Bruno et al. / Phytochemistry xxx (2013) xxx–xxx
64.4
24.2
a
In CDCl3. b In MeOD. c In DMSO-d6. d In acetone-d6. e In CDCl3/MeOD. f In CDCl3/pyridine-d5. g In CDCl3/DMSO-d6 9:1. h In CD2Cl2/DMSO-d6 7:1. i In pyridine-d5. j,k,,l,m Inverted with respect to the original paper. n Amended with
respect to the original paper. o As penta-acetate. p Not assigned in the original paper. q As tri-acetate. ⁄, ,# These values may be interchanged.
1
Negrete et al. (1984); 2Hsu HF et al. (2009); 3Marco et al. (1994); 4Hibasami et al. (2003); 5Choi et al. (2005); 6Youssef and Frahm (1994b); 7Marco et al. (1993); 8Daniewski et al. (1993); 9Vajs et al. (1999); 10Bentamane et al.
(2005); 11Buděšinský and Šaman (1995); 12Marco et al. (1992); 13Fernandez et al. (1989); 14Helal et al. (1997); 15Stevens (1982); 16Stevens and Merrill (1985); 17Meragelman et al. (1998); 18Wang et al. (1991); 19Collado et al.
(1987); 20Gonzalez Collado et al. (1986b); 21Li and Jia (1989); 22Negrete et al. (1988b); 23Khan et al. (2005a); 24Li et al. (2008); 25Santos et al. (1988); 26Zha and Hou (2008); 27Berdin et al. (1999); 28Hamburger et al. (1993); 29Bruno
et al. (2005a); 30Appendino et al. (1986); 31Youssef and Frahm (1994a); 32Stevens et al. (1991); 33Khan et al. (2004a); 34Dai et al. (2001); 35Youssef (1998); 36Stevens and Wong (1986); 37Öksük et al. (1994); 38Öksük and Topçu
(1994); 39Berdin et al. (2001); 40Rosselli et al. (2006b); 41Medjroubi et al. (1997); 42Khan et al. (2004b); 43Sosa et al. (1989); 44Yayli et al. (2006); 45Navarro et al. (1990); 46Jang et al. (2000); 47Krishna Kumari et al. (2003); 48Ahmed
et al. (1990); 49Lee et al. (2003); 50Ibrahim et al. (2010); 51Bernhard et al. (1979); 52Medjroubi et al. (2003b); 53Chicca et al. (2011); 54Fontana et al. (2007).
47
Please cite this article in press as: Bruno, M., et al. Sesquiterpenoids in subtribe Centaureinae (Cass.) Dumort (tribe Cardueae, Asteraceae): Distribution, 13C
NMR spectral data and biological properties. Phytochemistry (2013), http://dx.doi.org/10.1016/j.phytochem.2013.07.002
7
8
9
10
11
12
13
14
15
10
20
30
40
100
200
300
400
500
600
700
48
M. Bruno et al. / Phytochemistry xxx (2013) xxx–xxx
Table 11
H1 NMR diagnostic signals of guaionolides with epimeric side chains.
Ha
14
Hb
X
3'
H13b
H14b
H30 a
H30 b
H40
solv.
Ref.
5.58
4.97
3.17
2.82
1.62
CDCl3
Daniewski et al. (1993)
5.57
4.98
3.17
2.83
1.62
CDCl3
Bruno et al. (2005a)
5.59
5.56
5.71
4.96
4.96
4.92
3.01
3.15
3.16
2.85
2.81
2.82
1.57
1.60
1.60
acetone-d6
CDCl3
CDCl3
Bruno et al. (2005a)
Hamburger et al. (1993)
Hamburger et al. (1993)
5.57
4.84
3.17
2.81
1.61
CDCl3
Hamburger et al. (1993)
5.74
4.79
3.17
2.82
1.60
CDCl3
Hamburger et al. (1993)
5.64
4.98
3.17
2.83
1.62
CDCl3
Bruno et al. (2005a)
5.86
4.97
3.19
2.82
1.62
CDCl3
Öksük and Topçu (1994)
5.60
5.10
3.90
3.65
1.50
CDCl3
Gonzalez et al. (1978b)
3.88
3.91
4.18
3.96
3.65
3.73
4.06
3.77
1.56
1.54
1.55
1.55
CDCl3
CDCD3
Pyridine-d5
acetone-d6
Bruno
Bruno
Bruno
Bruno
3.87
4.10
3.63
4.00
1.55
1.70
CDCl3
pyridine-d5
Hamburger et al. (1993)
Berdin et al. (1999)
OR
H
4'
O
O
H
13
O
O
161
Hb
Ha
15-Desoxyrepin
H
O
HO
O
H
O
O
O
209
Repin
H
O
HO
O
O
H
O
O
O
210
Subteolide
H
O
HO
O
O
H
O
O
O
222
Solstiziolide
H
HO
O
O
HO
Cl
H
O
O
O
223
Episolstiziolide
H
HO
O
O
HO
Cl
H
O
O
O
244
Babylin B
H
O
HO
O
HO
HO
H
O
O
O
245
15-Deschloro-15-hydroxy-episolstiolide
H
O
HO
O
HO
HO
H
O
O
O
164
Linochlorin B
Cl
H
OH
HO
O
H
O
O
O
212
Acroptilin
Cl
H
OH
HO
O
O
H
5.57
5.71
5.85
5.66
et
et
et
et
al.
al.
al.
al.
(2005a)
(2005a)
(2005a)
(2005a)
O
O
O
224
Centaurepensin
Cl
H
HO
HO
Cl
OH
O
H
5.57
5.75
5.00
5.07
O
O
O
Please cite this article in press as: Bruno, M., et al. Sesquiterpenoids in subtribe Centaureinae (Cass.) Dumort (tribe Cardueae, Asteraceae): Distribution, 13C
NMR spectral data and biological properties. Phytochemistry (2013), http://dx.doi.org/10.1016/j.phytochem.2013.07.002
49
M. Bruno et al. / Phytochemistry xxx (2013) xxx–xxx
Table 11 (continued)
Ha
14
Hb
X
3'
H13b
H14b
H30 a
H30 b
H40
solv.
Ref.
5.83
4.81
3.87
3.63
1.55
CDCl3
Hamburger et al. (1993)
5.64
5.04
3.87
3.65
1.56
CDCl3
Bruno et al. (2005a)
5.87
4.91
3.87
3.64
1.55
n.r.
Öksük and Topçu (1994)
5.60
5.02
3.90
3.65
1.55
CDCl3
Gonzalez et al. (1978b)
5.74
5.04
4.07
3.97
1.67
pyridine-d5
Berdin et al. (1999)
5.60
5.12
3.88
3.64
1.42
CDCl3
Bruno et al. (2005a)
5.60
5.09
3.87
3.64
1.40
CDCl3
Öksüz and Putun (1983)
5.90
5.91
3.86
3.78
3.61
3.57
1.34
1.34
CDCl3
n.r.
Navarro et al. (1990)
Fernandez et al. (1987)
6.07
3.82
3.61
1.34
CDCl3
Navarro et al. (1990)
3.76
3.44
1.40
Acetone-d6
Gonzalez et al. (1974b)
OR
H
4'
O
O
H
13
O
O
225
Hb
Ha
17-epi-centaurepensin
Cl
H
HO
OH
O
HO
Cl
H
O
O
O
246
Cebellin J
Cl
H
OH
HO
O
HO
HO
H
O
O
O
249
Epicebellin J
Cl
H
OH
HO
O
HO
HO
H
O
O
O
247
Linochlorin C
Cl
H
OH
AcO
O
HO
H
HO
O
O
O
248
Rhaposerine
Cl
H
HO
OH
O
HO
H
AcO
O
O
O
211
Babylin A
OH
H
OH
HO
O
O
H
O
O
O
167
17,18-dihydroxy-aguerin A
OH
H
OH
HO
O
H
O
O
O
166
(20 S)-17,18-dihydroxy-aguerin A
OH
H
OH
HO
O
H
O
O
O
266
Grosheimin-20 ,30 -dihydroxy-isobutyrate
OH
H
O
OH
O
H
O
O
O
228
Chlorohyssopifolin D
HO
HO
Cl
5.73
OH
H
OCH CH
2
O
H
4.90
3
O
O
O
(continued on next page)
Please cite this article in press as: Bruno, M., et al. Sesquiterpenoids in subtribe Centaureinae (Cass.) Dumort (tribe Cardueae, Asteraceae): Distribution, 13C
NMR spectral data and biological properties. Phytochemistry (2013), http://dx.doi.org/10.1016/j.phytochem.2013.07.002
50
M. Bruno et al. / Phytochemistry xxx (2013) xxx–xxx
Table 11 (continued)
Ha
14
Hb
X
3'
H13b
H14b
H30 a
H30 b
H40
solv.
Ref.
5.70
5.01
3.86
3.56
1.39
Acetone-d6
Gonzalez et al. (1974b)
OR
H
4'
O
O
H
13
O
O
227
Hb
Ha
Chlorohyssopifolin E
OH
H
HO
HO
Cl
OH
O
H
O
O
O
Table 12
Other sesquiterpenes isolated from taxa of the Subtribe Centaureinae.
No
Structure
285
Name
Taxa
Ref.
4,9-Dioxo-bisabol-2,7(14),10-triene
Centaurea calcitrapa
Jakupovic et al. (1986)
4,9-Dioxo-bisabol-2,7E,10-triene
Centaurea calcitrapa
Jakupovic et al. (1986)
Carabrone
Serratula latifolia
Rustaiyan and Feramarzi (1988)
O
O
286
O
O
287
O
O
O
H
potent anti-H. pylori activity, and the MIC was around 100–200 lg/
mL. However, costunolide had no inhibitory effect of H. pylori urease activity at the concentation used for the growth inhibition assay. The most used drugs for the treatment of H. pylori infection, i.e.
proton pump inhibitors (omeprazole, lansoprazole), affect the
inhibtion of H. pylori urease activity or the inhibition of H. pylori
survival by urease-independent mechanisms. Costunolide, apparently exploits the latter type mechanism (Park et al., 1997).
Antimicrobial tests on costunolide (1), isolated from Cosmos
caudatus, indicated a complete inhibitory activity against S. aureus
and Saccharomyces cerevisiae, partial inhibitory activity against B.
subtilis, slight inhibitory activity against C. albicans and negative
inhibitory activity against E. coli and P. aeruginosa at concentrations of 100 lg/mL and 1 mg/mL, respectively (Ragasa et al., 1997).
Antimicrobial properties of 13-acetyl solstitialin A (183), chlorojanerin (219) and centaurepensin (224) were screened against
both standard and the isolated strain of E. coli, P. aeruginosa, Enterococcus faecalis, S. aureus, C. albicans and Candida parapsilosis. All lactones displayed moderate antibacterial activity (Gürbuz et al.,
2006;Ozcelik et al., 2009).
The antimicrobial activities of chloroform extracts from the
weeds C. tweediei and Centaurea diffusa, and the main SLs isolated
from these species, onopordopicrin (8) and cnicin (19), respectively, were assayed. Results show that the chloroform extracts
from both Centaurea species possess antibacterial activities against
a panel of Gram+ and Gram bacteria. Remarkable antibacterial
activity against methicillin-resistant S. aureus was also measured
(Bach et al., 2011).
Santamarin (99), alantolactone (121), pseudoivalin (280) were
shown to have good antifungal activity against Trichophyton mentagrophytes and Microsporum cookei; 9a-hydroxypartenolide (28)
only against T. mentagrophytes (Picman, 1984). Compounds 129,
155 and 156 revealed good inhibitory activity against Aspergillus
niger, Aspergillus ochraceus, Cladosporium cladosporioides and Phomopsis helianthi (Vajs et al., 1999).
The in vitro antifungal activity of compounds 8, 14, 15, 19, 20,
22, 24, 36, 75, 80–82, 94, 103, 107–109, 111, 137, 138 was tested
against nine fungal species, using the micro-dilution method. All
the compounds tested showed great antifungal activity comparable and sometimes better than miconazole used as control (Skaltsa
et al., 2000a; 2000b).
The activity against the fungus Cunninghamella echinulata of
compounds 1, 4, 19 and 142 has been evaluated. Compounds 4
and 19 were inactive whereas 1 and 142 showed the same noticeable EC50 values (6 lg/mL) close to that of ketokonazole (1.5 lg/
mL) used as reference drug (Barrero et al., 2000).
Costunolide (1), dehydrocostus lactone (142), zaluzanin C (147)
and 3-desoxysolstitialin A (180) were tested for their fungicidal
activity against the phytopathogenic fungi Colletotrichum acutum,
Colletotrichum fragariae, Colletotrichum gloesporioides,Fusarium oxysporum,Botrytis cinerea and Phomopsis ssp. Active compounds in
decreasing order of activity were 142, 1 and 147, whereas 180
was not active (Wedge et al., 2000).
The in vitro antifungal activity of four of the 10 sesquiterpenes
isolated from Centaurea deusta was tested against nine fungal
species (Aspergillus ssp., Penicillum ssp., Trichoderma viride,
C. cladosporioides, Alternaria alternata). Compounds 24, 81, 95,
and 112 showed greater antifungal potential than miconazole except against C. cladosporioides. The antibacterial bioassays showed
an activity only for compound 19 (Karioti et al., 2002). Nevertheless, this germacrane has also been proved to be active against
the same previous nine fungi with a fungicidal potential higher
Please cite this article in press as: Bruno, M., et al. Sesquiterpenoids in subtribe Centaureinae (Cass.) Dumort (tribe Cardueae, Asteraceae): Distribution, 13C
NMR spectral data and biological properties. Phytochemistry (2013), http://dx.doi.org/10.1016/j.phytochem.2013.07.002
51
M. Bruno et al. / Phytochemistry xxx (2013) xxx–xxx
Table 13
Occurrence of sesquiterpenoids in taxa of the Subtribe Centaureinae.
Taxa
Only germacranes
Aegialophila pumila (syn. Centaurea
aegialophila Sect. Aegialophila)
Centaurea affinis
C. aggregata
C. alba
C. alba ssp. caliacrae
C. alba ssp. deusta
C. alexandrina
C. aplopea
C. aplopea ssp lunensis
C. araneosa (a.n. C. procurrens)
C. arenaria
C. arenaria ssp. majorowii
C. arenaria ssp. odessana
C. aspera ssp. scorpiurifolia
C. attica ssp. drakiensis
C. attica ssp. ossaea
C. bombycina
C. calolepis
C. calvescens
C. cineraria
C. cineraria var. circae
C. coronopifolia
C. crithmifolia
C. crocodylium
C. cuneifolia ssp. pallida
C. derventana
C. diffusa ssp. brevispina = C. bovina
C. eriophora
C. friderici
C. gigantea
C. glaberima
C. glomerata
C. granatensis
C.
C.
C.
C.
C.
C.
C.
C.
C.
C.
C.
C.
C.
C.
C.
C.
C.
C.
C.
C.
grisebachi ssp. confusa
iberica
kartschiana
leucophaea
lusitanica
maculosa
mantoudii
mariolensis
maroccana (a.c.C. sulphurea)
micranthos
monticala
ovina
pallescens
pallidior
paniculata
pelia
polyacantha
pontica
pseudomaculosa
raphanina ssp. mixta
C.
C.
C.
C.
C.
rhenana ssp. savranica
rocheliana
rothmalerana
seridis
sonchifolia
C. splendens
C. squarrosa
C. sulphurea
Section or Subgenus
Germacanes
Gr. 6
4, 19
Egypt
Gr. 7, Acrolophus
Gr. 7, Acrolophus
Gr. 7, Phalolepis
Gr. 7, Phalolepis
Gr. 7, Phalolepis
Gr. 7, Calcitrapa
Gr. 7, Acrolophus
Gr. 7, Acrolophus
Gr. 7,Calcitrapa
Gr. 7, Acrolophus
Gr. 7, Acrolophus
Gr. 7, Acrolophus
Gr. 7,Seridia
Gr. 7, Acrolophus
Gr. 7, Acrolophus
Gr. 7, Acrolophus
Gr. 7, Acrolophus
Gr. 7, Acrolophus
Gr. 7, Acrolophus
Gr. 7, Acrolophus
Gr. 1, Stizolphus
Gr. 7, Acrolophus
Gr. 6, Crocodylium
Gr. 7, Acrolophus
Unresolved
classification
Gr. 7, Acrolophus
Gr. 7, Seridia
4, 19
19
4, 19, 21, 24, 36
4
4
19
19
19
19
19
19
19
4, 5, 19, 21
19
19
4, 19, 24
19
19
19
19
31, 32, 34, 35
4
4, 19
19
4, 19, 21, 24
Serbia
Polonia ??
Spain
Bulgaria
Italy
Egypt
Italy
Italy
Egypt
Hungary
Ukraine
Germany
Spain
Greece
Greece
Spain
Turkey
Germany
Italy
Italy
Turkey
Italy
Poland
Greece
Serbia
19
4, 19
Gr. 7, Acrolophus
Cynaroides
Unresolved
classification
Unresolved
classification
Gr. 7, Acrocentron,
syn. Colymbada
Gr. 7,Acrolophus
Gr. 7, Calcitrapa
Gr. 7, Acrolophus
Gr. 7, Acrolophus
Gr. 7, Seridia
Gr. 7, Acrolophus
Gr. 7, Acrolophus
Gr. 7, Acrolophus
Gr. 7, Calcitrapa
Gr. 7, Acrolophus
Gr. 7, Acrolophus
Gr. 7, Acrolophus
Gr. 7, Acrolophus
Gr. 7, Acrolophus
Gr. 7, Acrolophus
Gr. 7, Acrolophus
Gr. 7, Seridia
Gr. 7, Calcitrapa
Gr. 7, Acrolophus
Gr. 7, Acrocentron,
syn. Colymbada
Gr. 7, Acrolophus
Gr. 7, Jacea
Gr. 7, Acrolophus
Gr. 7, Seridia
Gr. 7, Seridia
4
9, 13
19
Greece
Poland,
France
Italy
Turkey
Montenegro
15, 17, 39, 43
Egypt
19
Spain
19
4, 19
19
19
3, 5, 19
19
19
19, 21
4, 19, 21, 36
19
19, 21
19
19
19
4
19
53, 54
4
4, 19
19
Greece
Uzbekistan
Italy
Italy
Portugal
USA
Greece
Spain
Morocco
?’
Spain
Poland
Egypt
Greece
France
Greece
??
Romania
Kazakhstan
Greece
19
19
19
53, 54, 57
8, 53, 54
Greece
Rep. Czeka
Portugal
Spain
Spain,
Greece
Montenegro
Uzbekistan
Spain,
Morocco
Algeria
Gr. 7, Phalolepis
Gr. 7, Acrolophus
Gr. 7,Solstitiaria
19
19
19
19, 64, 66
Elemanes Eudesmane Guaianes
Other Collection
place
(continued on next page)
Please cite this article in press as: Bruno, M., et al. Sesquiterpenoids in subtribe Centaureinae (Cass.) Dumort (tribe Cardueae, Asteraceae): Distribution, 13C
NMR spectral data and biological properties. Phytochemistry (2013), http://dx.doi.org/10.1016/j.phytochem.2013.07.002
52
M. Bruno et al. / Phytochemistry xxx (2013) xxx–xxx
Table 13 (continued)
Taxa
Section or Subgenus
Germacanes
C. transiens
C. tymphaea
C. thymphaea ssp. brevispina
C. vallesiaca
C. weldeniana
Stizolophus balsamita
Zoegea baldshuanica
Gr.
Gr.
Gr.
Gr.
Gr.
Gr.
Gr.
19
19
19
19
4
27, 29, 32, 33, 34, 35, 47, 56
28
7,
7,
7,
7,
7,
1
1
Acrolophus
Acrolophus
Acrolophus
Acrolophus
Jacea
Elemanes Eudesmane Guaianes
Other Collection
place
Greece
Greece
Greece
Italy
Italy
Kazakhstan
Poland
Germacranes and elemanes
Centaurea aegialophila (a.n. Aegialophila
pumila)
C. amara
C. aspera
Gr. 6
19
69, 80
Cyprus
Gr. 7, Jacea
Gr. 7, Seridia
10, 40
69, 84
4, 5, 8, 19, 21, 24, 36, 37, 38 94
C. aspera ssp. stenophylla
Gr. 7, Seridia
69, 84,
97
71
80, 84
Spain
Spain,
France
Spain
C. brugueriana
C. calcitrapa
4, 5, 8, 11, 16, 18, 19, 21, 24,
38, 58
Gr. 7, Tetramorphaea 19
Gr. 7, Calcitrapa
4, 19, 21, 36, 49
285,
286
C.
C.
C.
C.
castellana
cineraria ssp. busambarensis
cineraria ssp. umbrosa
cuneifolia
Gr.
Gr.
Gr.
Gr.
7,
7,
7,
7,
Acrolophus
Acrolophus
Acrolophus
Acrolophus
19, 53
19
19, 21
19
19
19, 21
8, 9, 19
69, 87
69, 80
80
69, 80
C. melitensis
C. napifolia
Gr. 7, Acrolophus
Gr. 7, Acrocentron,
syn. Colymbada
Gr. 7, Seridia
Gr. 7, Seridia
4, 8, 9
19, 21
C. nicaensis
Gr. 7, Seridia
8, 10, 19, 36, 40, 45
76, 84, 90
69, 80,
81, 84
84, 91
C. paniculata ssp. castellana
C. phrygia
Gr. 7, Acrolophus
Gr. 7, Jacea,
Lepteranthus
Gr. 7, Seridia
Gr.1
Gr. 7
19, 21
16
80
79
19, 21, 30, 53, 54
4, 6, 7, 8, 15
4, 16, 19, 21, 53
69, 81
75, 94
80
C. diffusa
C. eryngioides
C. sphaerocephala
Cheirolophus intybaceus
Cnicus benedictus
Germacranes, eudesmanes
Centaurea kurdica
C. stoebe
Gr. 7, Cynaroides
Gr. 7, Acrolophus
Phonus arborescens (a.n. Carthamus arb.)
Gr. 5
Germacranes, elemanes, eudesmanes
Centaurea achaia
Spain
Sicily
Sicily
Turkey
Serbia
Argentina
Egypt
81, 83
75
1, 2, 48
19
4, 19, 24
51, 52
Spain
Sicily
Sicily,
Algeria
Spain
Bulgaria
Sicily
Spain
100
102
139, 140,
141
C. aspera ssp. subinermis
Gr. 7, Acrocentron,
syn. Colymbada
Gr. 7, Seridia
C. attica
Gr. 7, Acrolophus
4, 7, 8, 13, 14, 15, 22, 36, 42 75,
94
5, 38
69,
92,
19, 21
80,
C. deusta
Gr. 7, Phalolepis
19, 20, 21, 24
C. grisebachi
Gr. 7, Acrolophus
4, 19, 24
80, 81,
95, 96
69, 80
C. malacitana
C. moesiaca
C. orphanidea
Gr. 7, Seridia
Gr. 7, Lepteranthus
Gr. 7, Acrolophus
4, 5, 10, 18, 19, 21
8, 16, 19, 20, 21, 24, 25, 26
4, 19, 21
69
80
80
C. paui
Gr. 7, Acrolophus
4, 19, 21, 24, 36, 59, 60, 61,
62, 64, 65, 67, 68
C. pullata
Gr. 7, Melanoloma
44, 45, 36, 46
C. spinosa
Gr. 7, Acrolophus
19, 21, 23
C. thessala ssp. drakiensis
C. zuccariniana
Neither germacranes nor guaianes
Centaurea. cadmea
C. granata
C. hierapolitana
Gr. 7, Acrolophus
Gr. 7, Acrolophus
19, 21, 24
19, 21
69, 70,
83, 85,
95
69, 84,
115, 117,
89
118, 119
80, 83, 95 109, 110,
111, 113
80, 81
103, 109
80
104
Gr. 7, Phalolepis
Gr. 7, Jacea
Gr. 7, Phalolepis
82,
84,
93
95
74, 77
Iran
Spain, Egypt
Argentina
Turkey
Serbia
Germany ??
Spain
107,
137
114,
135
109,
138
111,
108,
Greece
116,
Spain
111,
Greece
112
Greece
103,
110,
112
109
109,
103,
111
102
109,
111,
Greece
111
109,
122
115
130, 131
Spain
Bulgaria
Greece
Spain
Algeria
Greece
Greece
Greece
Turkey
Algeria
Turkey
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NMR spectral data and biological properties. Phytochemistry (2013), http://dx.doi.org/10.1016/j.phytochem.2013.07.002
53
M. Bruno et al. / Phytochemistry xxx (2013) xxx–xxx
C. phyllocephala
Unresolved
classification
Gr. 7, Tetramorphaea
Only guaianes
Acroptilon repens (syn. Centaurea repens)
Gr. 3
C. pamphilica
Amberboa divaricata
A. muricata (syn. Volutaria m., Centaurea
m.)
A. ramosa
Gr. 2
Gr. 2
A. tubuliflora
Centaurea adjarica (a.n. Psephellus
simplicicaulis)
Gr. 2
Gr. 1, Psephellus
C. aegyptiaca
Gr. 7, Calcitrapa
C. ainetensis (a.n. C. eryngioides)
Gr. 7, Acrocentron,
syn. Colymbada
Gr. 1, Plectocephalus
Gr. 7 or 1,
Microlophus, aff.
Sect. Centaurium
Gr. 7 or 1,
Microlophus, aff.
Sect. Centaurium
Gr. 1, Cheirolophus
C. americana
C. babylonica, (a.n. Centaurea behen)
C. behen (syn. Centaurium behen)
C. canariensis (a.n. Cheirolophus
canariensis)
C. clementei
C. collina
C.
C.
C.
C.
C.
debeauxii ssp. thuillieri
deflexa
depressa
floccose
helenoides
C. hermannii
C. hololeuca
C. hyrcanica
C. imperialis
C. isaurica
C. janeri
C. kandavanensis
C. kotschyi
C. marshalliana (a.n. Psephellus
marshallianus)
C. musimomum
C. nicolai
C. nigra
C. pabotii
C. phaeopappoides (a.n. Psephellus
phaeopapp.)
C. pseudosiniaca (a.n. C. sinaica)
Gr. 2
Gr. 7, Acrocentron,
syn. Colymbada
Gr. 7, Acrocentron,
syn. Colymbada
Gr. 7, Lepteranthus
Cheirolepis
Gr. 7, Cyanus
Gr. 7, Cyanus
Unresolved
classification
Unresolved
classification
Unresolved
classification
Gr. 7, Jacea
Gr. 7, Cynaroides
Unresolved
classification
Gr. 7,Jacea
Gr. 7, Acrocentron,
syn. Colymbada
Cheirolepis
Gr. 1, Psephellus
Unresolved
classification
Gr. 7, Acrocentron,
syn. Colymbada
Gr. 7, Jacea, sect.
Lepteranthus
Unresolved
classification
Gr. 1, Psephellus
Gr. 7, Calcitrapa
80, 81
133
Turkey
109
Iraq
149,
163,
208,
218,
234,
162
149,
151,
176,
209,
219,
255,
162,
198,
221,
261,
149,
162,
208,
216,
224,
246
149,
208,
218,
227
156
188,
217,
236,
262,
160,
169,
209,
218,
229,
160,
177,
212,
224,
267
162,
205,
214,
233,
162, 265, 269
189,
219,
240,
272,
162,
176,
212,
219,
233,
190,
220,
260,
273
271
207,
213,
222,
243,
162, 199, 206,
209, 214, 217,
219, 222, 224,
Caucasus
Argentina
India
Spain??
Pakistan
Egypt
Poland
Sinai
Lebanon
162
208, 209, 211, 212,
244, 246
Mexico
Lebanon
149, 160, 162, 183,
264, 277, 278
Iran
149, 158, 160, 162
Canary Is.
149, 162, 186, 187,
269, 279
149, 166, 190, 195
Spain
162
149,
181,
144,
162,
France
Turkey
Turkey
??
Turkey
162,
237,
162,
243,
209,
180,
229,
208
160, 162, 284
183
149
264
208,
241,
208,
244,
212,
181,
252
218,
242,
209,
246,
224
183,
219,
243
240,
256
224,
Spain
Turkey
Lebanon
Russia??
Iran??
Turkey
208, 219
150, 156
Spain
Iran
149, 162, 164, 167
208, 212, 219, 229
Turkey
Russia
160,
208,
224,
276,
150,
156
224
207,
219,
259,
Algeria
155,
Montenegro
162,
209,
225,
277,
152,
164,
218,
258,
278
153,
Spain
158, 165, 190
Iran
162, 208, 219
Armenia
250, 251
S. Arabia
(continued on next page)
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NMR spectral data and biological properties. Phytochemistry (2013), http://dx.doi.org/10.1016/j.phytochem.2013.07.002
54
M. Bruno et al. / Phytochemistry xxx (2013) xxx–xxx
Table 13 (continued)
Taxa
Section or Subgenus
C. ptosimopappa
Gr. 7, Ptosimopappus
C. ptosimopappoides
C. ragusina
Gr. 7, Ptosimopappus
Gr. 7, Acrocentron,
syn. Colymbada
Gr. 1, Rhaponticoides
C. ruthenica (a.n. Rhaponticoides
ruthenicus)
C. sinaica
Gr. 7, Calcitrapa
C. solstitialis ssp. shouwii
C. sventenii (a.n. Cheirolophus sventenii)
C. thracica
C. webbiana (a.n. Cheirolophus webbianus)
Centaurothamnus maximus
Chartolepis biebersteinii (a.n. Centaurea
pterocaula)
C. glastifolia (a.n. Centaurea glastifolia)
Gr. 7, Chartolepis
C. intermedia (a.n. Centaurea chartolepis)
C. pterocaula (a.n. Centaurea pterocaula)
Gr. 7, Chartolepis
Gr. 7, Chartolepis
Cheirolophus junoniaus
C. metlesicsii
Gr.1
Gr.1
C. teydis
C. uliginosus
Gr.1
Gr.1
Grossheimia macrocephala (a.n. Centaurea
m.)
G. ossica (a.n. Centaurea polyphylla)
Leuzea longifolia
L. rhapontica ssp. helenipholia
L. rhaponticoides
Psephellus carthalinicus
Gr. 7
P. colchicus
Gr. 1
P. daghestanicus
Gr. 1
P. dealbatus
Gr. 1
P. declinatus
P. hypoleucus
P. karabaghensis
Gr. 1
Gr. 1
Gr. 1
P. leucophyllus
P. nogmovii
Gr. 1
Gr. 1
P. somcheticus
Gr. 1
P. taochius
Gr. 1
P. zangezuri
Gr. 1
Rhaponticum pulchrum
Gr. 3
R. serratuloides
Gr. 3
Serratula strangulata
Stemmamarca carthamoides
Gr. 4
Unresolved
classification
Unresolved
classification
Unresolved
classification
S. rhapontica
Tricholepis glaberrima
Germacanes
Gr.
Gr.
Gr.
Gr.
Gr.
Gr.
Gr.
Gr.
Gr.
Gr.
Gr.
7, Solstitiaria
1, Cheirolophus
7, Microlophus
1, Cheirolophus
6 Rhaponticum
7, Chartolepis
7
3
3
3
1
Guaianes, germacranes
Amberboa lippii
Gr. 2
19
Centaurea africana (a. n. Rhaponticoides a.) Gr. 1, Rhaponticoides 19
Elemanes Eudesmane Guaianes
147,
190,
278
162,
149,
Other Collection
place
148, 149, 162,
199, 208, 219,
Turkey
190
160, 162
Turkey
Egypt
264
Caucasus
200, 208, 219, 224,
275
160, 162, 277
149, 160, 162
162, 208, 219
270
162, 208, 219
162, 208, 209, 212,
219, 224, 238
160, 162, 169, 207,
208, 209, 212, 218,
219, 223, 224, 225,
229, 238, 241, 245,
246, 249, 254, 264
162, 264
162, 208, 209, 212,
219, 224, 229, 238,
264
149, 158, 162, 190
158, 159, 190, 191,
199
158, 160, 162, 190
149, 160, 162, 190,
193, 194
149, 157, 160, 162,
263, 264, 269
264
201, 202, 203, 204
162, 208, 219
162, 208, 219
161,162, 164, 208,
209, 212, 224
161,162, 164, 208,
209, 212, 224
161,162, 164, 208,
209, 212, 224
161,162, 164, 208,
209, 212, 224
161, 162, 164
161, 162, 164
161,162, 164, 208,
209, 212, 224
161, 162, 164
161,162, 164, 208,
209, 212, 224
161,162, 164, 208,
209, 212, 224
161, 164, 208, 209,
212, 224
161,162, 164, 208,
209, 212, 224
160, 162, 176, 207,
208, 219, 233, 240,
243
162, 176, 212, 224,
239, 246, 248, 257
224, 226
162, 176, 208, 219,
233
162, 208, 219
Qatar
Sicily
Canary Is??
Bulgaria
Canary Is.
S. Arabia
Caucasus
Caucasus,
Turkey
Caucasus
Caucasus
Canary Is.
Spain
Canary Is.
Spain
Russia
Georgia
Portugal
Poland??
Poland??
Romania
Germania
France
Italy
Bielorussia
Romania
Armenia
Romania
?????
Hungary
Hungary
Belgium
Biolorussia
Kazakhstan
China
Poland??
??
162, 190
North India
264, 269, 275
162
Canary Is.
Algeria
Please cite this article in press as: Bruno, M., et al. Sesquiterpenoids in subtribe Centaureinae (Cass.) Dumort (tribe Cardueae, Asteraceae): Distribution, 13C
NMR spectral data and biological properties. Phytochemistry (2013), http://dx.doi.org/10.1016/j.phytochem.2013.07.002
55
M. Bruno et al. / Phytochemistry xxx (2013) xxx–xxx
C. bella (a.n. Psephellus bellus)
Gr. 1, Psephellus syn. 50
Sect. Hyalinella
C. exarata
C. incana
Gr. 7,Acrolophus
Gr. 7,Acrolophus
161,
173,
178,
209,
218,
229,
253
162
19
8
162,
174,
179,
212,
219,
233,
169,
175,
207,
213,
222,
243,
Germany
172,
176,
208,
216,
224,
246,
Spain
Morocco
Algeria
207, 208, 210, 212,
223, 238
C. scabiosa
Gr. 7, Acrocentron,
syn. Colymbada
C. scoparia
Gr. 7,
8
Pseudophaeopappus
C. solstitialis
Gr. 7, Solstitiaria
Guaianes, eudesmanes
Centaurea arguta (a.n. Cheirolophus teydis)
C. canariensis var. subexpinnata (a.n.
Cheirolophus canariensis var.
subexpinnata)
C. conifera (a.n. Leuzea conifera)
55
Rep Czeka
Gr. 1 Cheirolophus
Gr. 1, Cheirolophus
127, 129
128
Gr. 3, Leuzea
132
Gr. 7, Jacea
106
C. linifolia
Gr. 7, Jacea
106
C. ornata
99, 120
Cheirolophus sempervirens
Gr. 7, Acrocentron,
syn. Colymbada
Gr. 7, Jacea, sect.
Lepteranthus
Gr.1
Raponticum uniflorum
Serratula latifolia
Gr. 3
Gr. 4
Guaianes, germacrane, eudesmanes
Centaurea acaulis
99, 100
101, 126,
128
134
121, 122,
124
C. tweediei (a.n. Plectocephalus tweediei)
Cheirolophus x hortigenus
1
Gr. 7, Acrocentron,
syn. Colymbada
Gr. 1, Plectocephalu s 8, 63
Gr.1
7, 8
C. mauritanicus
Gr.1
6
Gr. 1 Cheirolophus
12, 41
Gr. 7, Acrocentron,
syn. Colymbada
4, 57
Guaianes, germacrane, elemanes
Centaurea. arbutifolia (a.n. Cheirolophus
arb.)
C. salonitana
C. tagananensis (a.n. Cheirolophus
tagananensis)
Guaianes, elemanes
C. chilensis (a.n. Plectocephalus chilensis)
Gr. 1, Cheirolophus
209,
162,
171,
208,
219,
231,
243
264
168,
197,
213,
224,
232,
169,
199,
217,
229,
235,
149,
181,
206,
210,
222,
229,
161,
182,
207,
212,
223,
162,
183,
208,
218,
224,
164,
190,
209,
219,
225,
160,
143,
160,
188,
162
145, 146, 149,
162, 184, 185,
189, 190
Siberia
Egypt
32, 55
C. hyssopifolia
C. uniflora ssp. nervosa
162,
149,
170,
206,
218,
230,
240,
8
69, 86
75, 84
Gr. 1, Plectocephalus
Spain
Sicily
210, 219,
240,
217, 224,
Spain
162,
218,
246,
166,
Spain
164,
224,
247
264,
Spain
215
Italy
143, 147, 158, 162
160, 162, 224
280, 281, 282, 283
Portugal
287
China
Iran
148, 150, 154
Algeria
105, 136
108, 126
268
143, 147, 149, 160,
162
149, 158, 162, 165,
190, 191, 192
Argentina
Spain
158
Canary Is.
150, 152, 156, 158,
161, 164, 190, 200
Bulgaria,
Serbia
Greece,
Turkey
Turkey
Canary Is.
149, 162
142, 143, 144, 149,
196
72, 73
Canary Is.
Canary Is.
98, 99
123, 124,
125
78, 88
208, 209,
224, 225,
244(245)
162, 212,
227, 228
149, 160,
212, 217,
227, 228,
149, 162,
266
208, 213,
Georgia
Argentina
France,
Bulgaria
Morocco
Chile
Chile
Gr. = group; a.n. = accepted name.
Please cite this article in press as: Bruno, M., et al. Sesquiterpenoids in subtribe Centaureinae (Cass.) Dumort (tribe Cardueae, Asteraceae): Distribution, 13C
NMR spectral data and biological properties. Phytochemistry (2013), http://dx.doi.org/10.1016/j.phytochem.2013.07.002
56
M. Bruno et al. / Phytochemistry xxx (2013) xxx–xxx
Fig. 3. Clusters based on presence/absence of single sesquiterpene in the Psephellus.
than miconazole (Panagouleas et al., 2003) and to inhibit mycelia
growth of B. cinerea and Fusarium moniliforme (Adekenov et al.,
1986a).
Alantolactone (121) was examined for activity against 16 species of fungi. At 10 lg/mL, the lactone strongly inhibited the
growth of M. cookei, T. mentagrophytes, and Trichothecium roseum
(Picman, 1983b). At the MIC of 1–5 ppm, it significantly inhibited
growth of four isolates of Fusarium graminearum and two of each
of Verticillium albo-atrum and Leptosphaeria maculans (Picman
and Schneider, 1993). Furthermore, it completely inhibited the
growth of T. mentagrophytes, Microsporum canis, Paecilomyces liacinus and Rhizotonia at 30, 40, 70, and 80 lg/mL, respectively. Complete inhibition of spore germination of Fusariumwas recorded at
400 lg/mL (Wahab et al., 1981).
The antifungal activity of costunolide (1) was assessed using the
mycelial radial growth inhibition technique against six plant pathogenic fungi (A. alternata, Helminthosporium spp., Nigrospora spp., F.
oxysporum, F. culmorium and Rhizocotonia solani). Costunolide
showed the strongest antifungal activity against three fungi,
Nigrospora spp., R. solani, and Helminthosporium spp. with EC50
values of 0.48, 2.92, and 2.96 lg/mL, respectively (Ahmed and
Abdelgaleil, 2005). Dehydrocostus lactone (142), isolated from a
dichloromethane extract of the Portuguese liverwort Targionia lorbeeriana, presented antifungal activity against Cladosporium
cucumerinum and C. albicans(Neves et al., 1999).
The antifungal sesquiterpene acid, isocostic acid (123), was isolated from Inula viscosa leaves, exhibited antifungal activity against
six species of dermatophytes, but was devoid of antibacterial activity. The mouse oral LD50 values for it were 1 g/kg, with a favorable
therapeutic index of 100 (Shtacher and Kashman, 1970).
Phytochemical investigation of Vernonia arborea resulted in
the isolation of zaluzanin D (148). It showed 100% inhibition
in mycelia growth of R. solani, the effect being ca. 75% with
Curvularia lunata and B. cinerea at 200-ppm concentration (Kunari et al., 2003).
4.2. Antiprotozoal
Cynaropicrin (162), isolated from Moquinia kingii was evaluated
in vitro against Trypanosoma cruzi trypomastigotes and the IC50 values for trypanocidal activity was 93.5 lg/mL (Schinor et al., 2004).
Stizolin (27), alantolactone (121), cynaropicrin (162), repin
(209), acroptilin (212) and centaurepensin (224) showed strong
protozoacidal activity in vitro (active at 0.24–7.8 lg/mL) against
Entamoeba histolytica and Trichomonas vaginalis. The presence of
an exocyclic methylene ring conjugated with the lactone carbonyl,
the presence of an acetyl group on the ring, or oxidation of a hydroxyl group to a keto group generally increased the protozoacidal
activity of the sesquiterpenes (Rubinchik et al., 1976).
The AcOEt extract of the bark of Michelia alba D.C. (Magnoliaceae) exhibited killing activity against T. cruzi. A bioassay-guided
purification afforded several trypanocidal constituents, among
which costunolide (1) and santamarine (99). The minimum lethal
concentrations of these compounds against epimastigotes of T. cruzi were 7 lM and 25 lM, respectively (Asaruddin et al., 2003). Also
dehydrocostus lactone (142) and zaluzanin D (148) showed lethal
activity against epimastigotes of T. cruzi at concentrations of 6.3
and 2.5 lM, respectively (Uchiyama et al., 2002).
Costunolide (1), b-cyclocostunolide (98) and dehydrocostus
lactone (142) showed significant antitrypanosomal activity against
T. brucei with EC50 of 0.066, 0.18 and 0.21 lg/mL, respectively,
several-fold more potent than the antitrypanosomal drugs eflornithine and suramin (Otoguro et al., 2011).
The essential oil of Echinops kebericho, containing as major
constituent dehydrocostus lactone (142), exerted strong
antileishmanial activity activity against two Leishmania
Please cite this article in press as: Bruno, M., et al. Sesquiterpenoids in subtribe Centaureinae (Cass.) Dumort (tribe Cardueae, Asteraceae): Distribution, 13C
NMR spectral data and biological properties. Phytochemistry (2013), http://dx.doi.org/10.1016/j.phytochem.2013.07.002
M. Bruno et al. / Phytochemistry xxx (2013) xxx–xxx
57
Fig. 4. Clusters of Acrolophus based on presence/absence of single sesquiterpene.
Please cite this article in press as: Bruno, M., et al. Sesquiterpenoids in subtribe Centaureinae (Cass.) Dumort (tribe Cardueae, Asteraceae): Distribution, 13C
NMR spectral data and biological properties. Phytochemistry (2013), http://dx.doi.org/10.1016/j.phytochem.2013.07.002
58
M. Bruno et al. / Phytochemistry xxx (2013) xxx–xxx
Fig. 5. Clusters based on presence/absence of structurally similar sesquiterpenes part A.
strains ( Leishmania aethiopica and Leishmania donovani) that
was even higher than that of amphotericin B (Tariku et al.,
2011).
Costunolide (1), isolated from the essential oils from heartwood
and sapwood of Eremanthus elaeagnus, Vanillosmopsis erythropappa
and Moquinea velutina was effective against infestation by Schisto-
Please cite this article in press as: Bruno, M., et al. Sesquiterpenoids in subtribe Centaureinae (Cass.) Dumort (tribe Cardueae, Asteraceae): Distribution, 13C
NMR spectral data and biological properties. Phytochemistry (2013), http://dx.doi.org/10.1016/j.phytochem.2013.07.002
M. Bruno et al. / Phytochemistry xxx (2013) xxx–xxx
59
Fig. 6. Clusters based on presence/absence of structurally similar sesquiterpenes part B.
soma mansoni when topically applied to the skin (Baker et al.,
1973).
In the course of searching for antiprotozoal agents from terrestrial plants, costunolide (1) was isolated from Magnolia sororum
using bioassay-guided fractionation methods. It exhibited activity
(IC50 = 9.4 lM) in vitro against the Leishmania mexicana parasite
but not against T. cruzi and Monkey vero (Sanchez et al., 2007).
Cnicin (19), reynosin (100), alantolactone (121), ivalin (122)
and carabrone (287) were tested in vitroagainst four major protozoan pathogens, T. brucei rhodesiense, T. cruzi, L. donovani as well
as Plasmodium falciparum. Cnicin displayed high anti-parasitic
activity against T. brucei rhodesiense (IC50 = 1.3 lM), while alantolactone was moderately active against all the four pathogens
(Schmidt et al., 2009).
Extracts from C. scabiosa L. aerial parts revealed evident antiopisthorchiasis activity. The most effective was the extract contained greater amount of SLs (cynaropicrin (162), repin (209) and
grosheimin (264) than other extracts (Kaminskii et al., 2010a,b).
12-Carboxy-3,11(13)-eudesmadiene (123), isolated from the
above-ground portions of I. viscosa, showed anthelmintic activity
against Hymenolepis nana var. fraterna and Syphacia obvelata
in vitro. However, its activity against these parasites in mice was
poor, due to considerable absorption in the digestive tract before
reaching the intestinal site of parasitization (Azoulay et al., 1986).
4.3. Anti-inflammatory
SLs are known to possess a considerable anti-inflammatory
activity in different inflammation models. They inhibit the transcription factor NF-jB, involved in the synthesis of inflammatory
mediators, such as cytokines and chemokines, probably by alkylating cysteine in the DNA binding domain of the p65 subunit.
Cynaropicrin (162), santamarine (99) and reynosin (100)
showed potent dose-dependent inhibitory effect on the production
of tumor necrosis factor-a (TNF-a) with an IC50 of TNF-a production were 2.86 lg/mL (8.24 lM), 26.2 lg/mL (105 lM), and
21.7 lg/mL (87.4 lM), respectively. In the case of cynaropicrin
(162) the result was better than dbcAMP and prednisolone used
as controls. Treatment with sulfydryl (SH) compounds such as
L-cysteine, dithiothreitol, and 2-mercaptoethanol abrogated the
inhibitory effect of cynaropicrin on TNF-a production showing that
Please cite this article in press as: Bruno, M., et al. Sesquiterpenoids in subtribe Centaureinae (Cass.) Dumort (tribe Cardueae, Asteraceae): Distribution, 13C
NMR spectral data and biological properties. Phytochemistry (2013), http://dx.doi.org/10.1016/j.phytochem.2013.07.002
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M. Bruno et al. / Phytochemistry xxx (2013) xxx–xxx
the bioactive moiety is the unsaturated lactone (Cho et al., 2000,
1998).
Cynaropicrin (162), aguerin B (160) and grosheimin (264)
showed a remarkable inhibitory effect on inducible nitric oxide
synthase with IC50 values in the range 1.5–9.5 lg/mL (Blunder
et al., 2008). Cynaropicrin (162) displayed immunomodulatory effects on the production of cytokine and nitric oxide from macrophages/monocytes. It has been demonstrated that cynaropicrin
may be a potent functional regulator of CD29 and CD98 via interrupting extracellular signal-regulated kinase (ERK) activation
which may be linked to cytoskeleton rearrangement, suggesting
further application to CD29- and CD98-mediated diseases such as
virus-induced chronic inflammation, and invasion, migration, and
metastasis of leukocyte (Cho et al., 2004a).
An investigation on a set of 103 different SLs representing six
structural groups (44 germacranolides, 16 heliangolides, 22 guaianolides, 9 pseudoguaianolides, 2 hypocretenolides, 10 eudesmanolides) for their NF-jB inhibiting properties was carried out and
the resulting IC100-values were submitted to a QSAR study. These
studies indicated that the SLs more active possessed a rigid skeleton (furanoheliangolides and guaianolides), whereas in the case of
flexible skeletons (germacranolides, such as germacrolides and
melampolides), inhibition might be mostly determined by the
number and type of a, b-unsaturated carbonyl structural elements
(Siedle et al., 2004).
A review on the roles of NF-jB in inflammation, photoaging,
and other diseases, on the inhibition of NF-jB by artichoke extract,
the identification of cynaropicrin (162) as an active ingredient of
artichoke extract and the prevention of pigmentation and photoaging, and decrease of open pores of the skin by lotions containing
artichoke extracts in humans has been reported (Banno, 2011).
Investigation of Podachaenium eminens afforded several SLs
from which costunolide (1) and santamarin (99) are new for this
plant. The isolated compounds were studied for their anti-inflammatory activity using NF-jB as a molecular target. NF-jB is involved in the synthesis of inflammatory mediators, such as
cytokines and chemokines. The compounds completely inhibited
NF-jB DNA binding in an electrophoretic mobility shift assay at
concentrations of 50 and 200 lM, respectively, without showing
any cytotoxic effects (Castro et al., 2000).
Nitric oxide (NO), derived from L-arginine, is produced by two
types (constitutive and inducible) of nitric oxide synthase (NOS:
cNOS and iNOS). The NO produced in large amount by the iNOS
is known to be responsible for inflammation, the vasodilation,
and hypotension observed in septic shock, and cancer metastasis.
Inhibitors of the overproduction of NO may thus be useful candidates for the treatment of inflammatory diseases. Dehydrocostuslactone (142) showed significant inhibitory activities on the
production of NO and release of TNF-a with IC50 values lower than
1 lM (Zhao et al., 2008).
Costunolide (1), santamarine (99), reynosin (100), dehydrocostus lactone (142) and zaluzanin C (147) were found to inhibit
NO production in lipopolysaccharide (LPS)-activated mouse peritoneal macrophages (IC50 = 1.2–3.8 lM). Furthermore, costunolide
and dehydrocostus lactone inhibited iNOS in accordance with
induction of heat shock protein 72 (HSP 72) (Matsuda et al.,
2000a, 2003; De Marino et al., 2005).
Costunolide (1), isolated from Magnolia grandiflora, was found
to inhibit NO production by down-regulating iNOS expression, at
least, in part through the inhibition of IjBs0 phosphorylation and
degradation, which are essential for the activation of NF-jB (Koo
et al., 2001). Furthermore, costunolide (1) showed an ability to inhibit expression of multiple neuroinflammatory mediators of NFjB
and MAPK activation. Further investigation of this novel role of
costunolide may aid in developing better therapeutic strategies
for treatment of neuroinflammatory diseases (Rayan et al., 2011).
The antipyretic and anti-inflammatory effects of costunolide (1)
were investigated. The oral administration of costunolide inhibited
carrageenan (Cg)-induced paw edema (ID50 0.18 (0.12–0.27) mg/
kg) and was effective in abolishing lipopolysaccharide (LPS)-induced fever (0.15 mg/kg) (Kassuya et al., 2009).
It was shown that the suppression of NO production by dehydrocostus lactone (142) is mediated by the inhibitory action on the
i-NOS gene expression through the inactivation of NF-jB and this
sesquiterpene lactone can act as a pharmacological inhibitor of
the NF-jB activation (3.0 lM better than pyrrolidine dithiocarbamate used as control) (Jin et al., 2000).
In order to elucidate the mechanism for the anti-inflammatory
activity of santamarin (99), its ability to interfere with the activation of the transcription factor NF-jB was studied. Santamarin
(99) showed a moderate inhibitory activity (Lyss et al., 2000).
Alantolactone (121), isolated from the roots of Inula racemosa
(Asteraceae), was screened for its inflammatory activity against
carrageenan induced paw edema and hepatoprotective activity
in vitro against galactosamine and thioacetamide and in vivo
against carbon tetrachloride, paracetamol and rifampicin induced
hepatotoxicities in albino rats. It showed significant anti-inflammatory and hepatoprotective activities similar to that of silymarin
(Kurma and Mishra, 1997).
Cynaropicrin (162) and 13-acetyl solstitialin A (183), both present in the aerial parts of the yellow star thistle (C. solstitialis) have
toxic potential in cell cultures of substantia nigra of the rat. The
specificity of action towards cells of the substantia nigra remains
to be proved, and a toxic action in the midbrain may contribute
to the nigro-pallidal encephalomalacia, caused by the ingestion
of the yellow star thistle by horses (Wang et al., 1991;Cheng
et al., 1992).
The mixture of elemanolides 72 and 73 from C. chilensis showed
anti-inflammatory activity when tested against carrageenan-induced edema in the guinea pig hindpaw (Negrete et al., 1993)
and desacylcynaropicrin (149) isolated from the aerial parts of
Cyclolepis genistoides produced a significant inhibition of carrageenan-induced inflammation at doses of 75 and 100 mg/kg,
respectively (Sosa et al., 2011). Cnicin (19) showed an anti-inflammatory activity in the rat paw edema screen which was nearly
equivalent to that of indomethacin (Schneider and Lachner, 1987).
Compounds 196 and 199 were evaluated for their inhibitory effects against cyclooxygenases-1 and 2 in vitro. Compound
199showed moderate COX-1-inhibiting activity with IC50 value of
78.8 lM, comparable to that of representative anti-inflammatory
drug aspirin with an IC50 value of 77.2 lM. Both compounds displayed potent COX-2 inhibitory activities with IC50 values of 28.7
and 57.9 lM, respectively, in comparison with that of aspirin with
an IC50 value of 87.6 lM (Wang et al., 2009).
4.4. Antitumor and cytotoxic
Several guianolides have been the object of many antitumor
and cytotoxic studies. For example, cynaropicrin (162) has been
shown to have cytotoxic effect against several types of cell lines
such as macrophages, eosinophils, fibroblasts and lymphocytes.
Cynaropicrin potently inhibited the proliferation of leukocyte cancer cell lines, such as U937, Eol-1 and Jurkat T cells, but some other
cells such as Chang liver cells and human fibroblast cell lines were
not strongly suppressed by cynaropicrin treatment. The cytotoxic
effect of cynaropicrin was due to inducing apoptosis and cell cycle
arrest at G1/S phase, according to flow-cytometric, DNA fragmentation and morphological analyses using U937 cells (Cho et al.,
2004b).
The same compound (162) along with desacylcynaropicrin
(149) and aguerin B (160) a were evaluated in vitro for cytotoxic
activity against human cancer cell lines, comprising SK-OV-3,
Please cite this article in press as: Bruno, M., et al. Sesquiterpenoids in subtribe Centaureinae (Cass.) Dumort (tribe Cardueae, Asteraceae): Distribution, 13C
NMR spectral data and biological properties. Phytochemistry (2013), http://dx.doi.org/10.1016/j.phytochem.2013.07.002
M. Bruno et al. / Phytochemistry xxx (2013) xxx–xxx
LOX-IMVI, A549, MCF-7, PC-3 and HCT-15 by the sulforhodamine B
(SRB) assay method. Compounds 160 and cynaropicrin (162)
showed the most potent cytotoxic activity against MCF-7 (IC50:
1.1 lg/mL) and HCT-15 cells (IC50: 0.9 lg/mL and 1.4 lg/mL,
respectively), whereas compound 149 showed a moderate activity
(IC50: 17.1 lg/mL) only against the HCT-15 cell line (Ha et al.,
2003).
The biological investigation on the anti-proliferative activity of
aguerin B (160) and the nor-guaianolide 284 was carried out
against human pancreatic and colon cancer cells. Of the two compounds, only aguerin B (160) was shown to induce apoptotic cell
death, confirming the role as pro-apoptotic moiety of the a-methylene-c-lactone ring present in 160 but not in 284 (Chicca et al.,
2011).
Desacylcynaropicrin (149), cynaropicrin (162), chlorojanerin
(219), chlorohyssopifolin A (224) and chlorohyssopifolin E (227)
have been tested for cytotoxic activities against human cervix
epitheloid carcinoma cell lines (HeLa) and human hepatoma cell
lines (SMMC-7721). The best activity was found for compound
162 with IC50 of 13.0 and 8.7 lg/mL, respectively (Ren et al., 2007).
The cytotoxicity of some of the above compounds (149, 160,
162) along with 169 and 190 was tested by SRB bioassay method
against five cultured human tumor cells (A549, SK-OV-3, SKMEL-2, XF-498, HCT-15). 160 and 162 showed non-specific significant cytotoxicity against these human tumor cell lines (160: 0.23–
1.72 lg/mL and 162: 0.29–1.37 lg/mL) comparable and sometimes
better than etoposide and doxorubicin used as comparison drugs
(Choi et al., 2005).
Cytotoxic studies with VERO cell cultures treated with deacylcynaropicrin (149), cynaropicrin (162), and grossheimin (264)
indicated that the IC50 values for the last two compounds were
5.5 and 4.2 lg/L, respectively (Piacentini et al., 1986, 1987).
Compounds 149 and 162 showed very potent cytotoxic activity
against tumor cell line P388 (murine leukemia), more than the natural anticancer agent pseudolaric acid B used as positive control, at
the IC50 levels of 0.36 and 0.01 lM, respectively (Zha and Hou,
2008). They were also tested against human cancer cell lines of
malignant melanoma (SK-MEL), epidermoid (KB), ductal (BT-549)
and ovarian (SK-OV-3) carcinomas for cynaropicrin (162), janerin
(208) and chlorojanerin (219), showing in vitro cytotoxic activity
with IC50 values of 2–6 lg/mL (Muhammad et al., 2003).
Grosshemin (264) and the germacranolide cnicin (19) had cytostatic action on HeLa cells with ID50 of 2.5 lg/mL and 0.1 lg/mL,
respectively. Dihydroestafiatone (270), on the other hand, showed
poor cytostatic action (Gonzalez et al., 1978a). Compounds 224,
217, 212, 228, 227, 162, and 149 were also tested for cytostatic action on HeLa cells: the first four exhibited an ID50 in the range
0.25–0.5 lg/mL (Gonzalez et al., 1980b). Furthermore, grosshemin
(264) inhibited the growth of malignant HeLa cultures. The effect
of the compound on an in vitro lymphocyte culture showed that
it inhibited cell division at the metaphase stage (Bialecki et al.,
1973). Grosshemin (264) also inhibited sarcoma 180, Pliss’s lymphosarcoma and Ehrlich solid tumor (Adekenov et al., 1986b).
The cytotoxic activity of the guaianolides 208, 209, 211, 212,
224, 244 and 246 against tumor cell replication (A549, MCF-7,
1A9, KB, KB-V, HCT-8, SK-MEL-2) was reported. Repin (209), chlorohyssopifolin C (212) and chlorohyssopifolin A (224) showed significant antitumor potency (Bruno et al., 2005c). Repin (209)
showed also significant activity toward chick embryo sensory neurons and a causal relationship between repin and the necrosis of
the neural cells in substantia nigra of horses leading to equine
nigrostriatal encephalomalacia (ENE) disease has been suggested
(Stevens et al., 1990). To understand the mechanism whereby
ingestion of Centaurea repens induces ENE and a Parkinson’s disease (PD)-like disorder, repin cytotoxicity was examined. Repin
was found to be highly cytotoxic to both Pc12 cells and mouse
61
astrocytes in a dose- and time-dependent way. The cytotoxic effects were accompanied by depletion of glutathione, a rise in the
level of reactive oxygen species and damage to cellular membranes
(Robles et al., 1997). Both A- an B-ring modifications of the electrophilic exocyclic methylene group and the epoxy-ester moiety were
performed, further demonstrating the importance of these functional group contributions to toxicity (Anand et al., 2003; Tukov
et al., 2004).
Zaluzanin C (147) showed a significant cytotoxicity against several tumor cell lines A549, SK-OV-3, SK-MEL-2, XF498, HCT15
(Choi et al., 2006), GTB, HL60 (Zidorn et al., 2004) and P-388 lymphocytic leukemia (Jolad et al., 1974), a moderate cytotoxicity
against three tumor cell lines (HepG2, HeLa, OVACAR-3) (Sun
et al., 2003), and revealed relatively high cytotoxicities on human
colon carcinoma cell lines and lung adenocarcinoma cell lines
(Ahn et al., 2006). Furthermore, it showed significant cell growth
inhibitory activity against murine lymphocytic leukemia (P388)
in vitro (Ando et al., 1982), and a capacity to inhibit protein synthesis in intact HeLa cells preferentially to DNA and RNA synthesis. On
the other hand dihydroestafiatone (270) showed poor cytostatic
action on HeLa cells (Gonzalez et al., 1978a). Zaluzanin C (147)
inhibits the proliferation of T and B lymphocytes of mice
in vitroexhibiting cytotoxicity at concentration of 10 lM or lower
(Chen et al., 2006).
Compounds 142, 147 and 190 isolated from Ainsliaea macrocephala were tested for inhibitory activity against the production of
nitric oxide in RAW 264.7 cells stimulated by LPS, as well as for
cytotoxicity against RAW 264.7 macrophages. Zaluzanin C (147)
strongly inhibited the production of nitric oxide with an IC50 value
of 2.5 lM, and simultaneously showed low cytotoxicity against
RAW 264.7 macrophages. The other two compounds had moderate
activity (Wu et al., 2011).
The molecular mechanism underlying the suppression of
lipopolysaccharide (LPS)/interferon-c (IFN-c)-induced nitric oxide
(NO) and prostaglandin (PGE2) production was investigated in
RAW 264.7 macrophages treated with sesquiterpene lactone,
zaluzanin-C (147). It decreased NO production in LPS/IFN-c-stimulated RAW 264.7 macrophages with an IC50 of about 6.6 lM and
3.8 lM, respectively. In addition, these compounds inhibited the
synthesis of PGE2 in LPS/IFN-c-treated RAW 264.7 macrophages.
Furthermore, treatment with zaluzanin C (147) resulted in a
decrease in inducible NO synthase (iNOS) and cyclooxygenase-2
(COX-2) protein and mRNA expression levels (Shin et al., 2005).
Salograviolide A (156) was found reduced the growth of colon
cancer cell lines (El-Najjar et al., 2008) and to exert significant
growth inhibitory effects on neoplastic cells. At concentrations that
were not cytotoxic to primary keratinocytes, it preferentially inhibited the proliferation of papilloma and squamous cell carcinoma
(SCC) cell lines without significantly affecting the growth of normal
cells (Ghantous et al., 2008). Furthermore it was shown to reverse
the effects observed by interleukin-I on cyclooxygenase-2 levels in
NF-kB translocation in intestinal epithelial cells. It reduces the level of inflammatory cytokines and the level of inflammation in
the animal model (Al-Saghir et al., 2009).
Also several sesquiterpenoids with a different skeleton rather
than guaiane have been studied for their cytotoxic and antitumor
activities.
Cnicin (19) showed cytotoxic activity against KB with
ED50 = 3.4 lg/mL (Vanhaelen-Fastre, 1972), against TXL-5 mice
lymphoma cells with ID50 = 6 lg/mL (El-Marsy et al., 1984) and
showed moderate antiproliferative effects against HeLa, and
A431 human tumor cell lines (Csapi et al., 2010). The cytotoxic
activities of some cnicin (19) and salonitenolide (4) derivatives
were determined against A549 and MCF-7 tumor cell lines. Cnicin
was selectively cytotoxic against the MCF-7 breast cancer cell line
with IC50 = 4.2 lM (Rosselli et al., 2010).
Please cite this article in press as: Bruno, M., et al. Sesquiterpenoids in subtribe Centaureinae (Cass.) Dumort (tribe Cardueae, Asteraceae): Distribution, 13C
NMR spectral data and biological properties. Phytochemistry (2013), http://dx.doi.org/10.1016/j.phytochem.2013.07.002
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The cytotoxic activities of chloroform extracts from the weeds
C. tweediei and C. diffusa, and the main SLs isolated from these species, onopordopicrin (8) and cnicin (19), respectively, were assayed. Both the extracts and the purified SLs show high
cytotoxicity against human-derived macrophages (Bach et al.,
2011). Onopordopicrin (8) also showed cytotoxic activity against
KB cell line (Lonergan et al., 1992).
The in vitro cytotoxic activity of germacranes 4, 5, 8, 19, 20 and
elemanes 69, 75 was investigated against P388, A549 (human non
small lung cancer) and HT29 (human colon cancer). As expected for
compounds with an a-methylene-c-lactone group, they have
cytotoxic activity with IC50 values ranging from 2 to 10 lg/mL.
The additional a, b-unsaturated ester group present in 8, 19, 20
and 75 increases the activity two or three times (Barrero et al.,
1995).
Also germacranes 19, 20, elemanes 75, 80, 94, and eudesmanes
103, 104, 111, 112 were examined for their in vitro cytotoxic/cytostatic activity against five human cell lines (i.e. DLD1, SF268, MCF7, H460, OVCAR3). Compounds 75 and 80 were found to be the
most active and exhibited a considerable growth-inhibiting activity against most of the cell lines tested (Koukoulitsa et al., 2002).
Cnicin (19), salitenolide (4) and the elemanes 66, 70, 80, 83 were
tested against nine cancer cell lines. 19 was active against 1A9,
KB and KB-VIN. 83 showed good activity for all the lines except
A549, and 66 and 70 were shown to be the best with IC50 < 1 lM
(Bruno et al., 2005b). Cnicin (19) showed inhibition of NF-jB and
inhibition of iNOS activity with IC50 values of 1.8 and 6.5 lM,
respectively. Cytotoxic activity of cnicin (19) was observed
toward pig epithelial (LLC-PK11), human malignant melanoma
(SK-MEL) and human ductal carcinoma (BT-549) (Baykan Erel
et al., 2011).
It has been suggested that deregulation of activin signaling contributes to tumor formation. Data suggested that alantolactone
(121) induced activin/SMAD3 signaling in human colon adenocarcinoma HCT-8 cells and that it performs its antitumor effect by
interrupting the interaction between Cripto-1 and the activin
receptor type IIA in the activin signaling pathway (Shi et al.,
2011). Furthermore, it showed antiproliferative activities against
MK-1, HeLa, and B16F10 cell lines with GI50 in the range 4.7–
6.9 lM (Konishi et al., 2002). Alantolactone (121) was also identified from the roots of Inula helenium L. and its inhibitory effects on
human non-small cell lung cancer (NSCLC) A549 cells was examinated. The antiproliferative effect of alantolactone on A549 cells
was investigated via MTT [30 -(4,5dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] assay and its apoptosis-inducing effect
was determined by Hoechst staining and flow cytometry. Alantolactone was found to significantly inhibit the proliferation of
A549 cells and to induce morphological changes typical for apoptosis (Zong et al., 2011).
9-a-Hydroxyparthenolide (28), isolated from Anvillea garcini,
has shown activity in both the 9 KB cell culture and P388 mouse
leukemia test systems (Tyson et al., 1981). Compound 28 was evaluated by an in vitro disease-oriented antitumor screen, which
determinates cytotoxic effects against a panel of approximately
60 human tumor cell lines. The best results were obtained for
NCI-H522 (non-small cell lung) and CCRF-CEM (leukemia) with
ED50 of 0.5 lg/mL and 0.84 lg/mL, respectively (Sattar et al.,
1996). Other authors tested the same compound against five other
human cancer lines showing an IC50 of 2 lg/mL for A549, H116 and
PSN1 (El Hassany et al., 2004).
The in vitro cytotoxic activities of 8a-(40 acetoxy-angeloyl)-salonitenolide (18) and malacitanolide (109) were assayed towards
P388 and Schabel mouse lymphomas and toward the A549 (lung
carcinoma), HT-29 (colon carcinoma) and MEL-28 (melanoma) human cell lines. Compound 18 showed an IC50 = 2.5 lg/mL against
both mouse lymphomas and an IC50 = 5 lg/mL towards the three
human cell lines whereas 109 showed an IC50 = 0.12 lg/mL in all
cases (Barrero et al., 1997a).
Stizolicin (32), solstitialin A (181) and xanthinin (288) demonstrated a limited antitumor action in vivo on two types of tumor:
L-1210 leukemia and P388 leukemia (Naidenova et al., 1988).
A moderate cytotoxic activity of compound 83 was also shown
against SF268 and OVCAR3 tumor cell lines (Saroglou et al., 2005).
Compounds 9 and 13 were shown to have a good cytotoxic
activity against colon cancer cell line CaCo-2 with IC50 values of
8.5 and 26.4 lM, respectively (Shoeb et al., 2007a).
Ivalin (122) showed cytotoxic activity (ED50 < 10 lM) against
A549, SK-OV-3, SK-MEL-2 XF-498 and HCT-15 tumor cell lines
comparable to that of cisplatin. Carabrone (287) was less active
(Lee et al., 2002). A very good cytotoxic activity was observed for
ivalin (122) against P388, KB-3 and KB-V1 with ED50 in the range
0.14–1.8 lg/mL (Topçu et al., 1993).
A large number of papers have been published on the biological
properties of costunolide (1) and dehydrocostuslactone (142).
Costunolide (1), isolated from the root of Saussurea lappa, was
investigated for its effects of on the induction of apoptosis in HL60 human leukemia cells (Kim et al., 2010) and its putative pathways of action. Using apoptosis analysis, measurement of reactive
oxygen species (ROS), and assessment of mitochondrial membrane
potentials, it was shown that costunolide is a potent inducer of
apoptosis, and facilitates its activity via ROS generation, thereby
inducing mitochondrial permeability transition (MPT) and cytochrome c release to the cytosol. ROS production, mitochondrial
alteration, and subsequent apoptotic cell death in costunolidetreated cells were blocked by the antioxidant N-acetylcysteine
(NAC) (Lee et al., 2001). Furthermore costunolide (1) was found
to induce apoptotic cell death in a dose-dependent manner by
nucleosomal DNA ladder and flow cytometric analysis. Immunoblot analysis showed that the level of the anti-apoptotic protein,
Bcl-2, was decreased, whereas the cleavage of poly-(ADP-ribose)
polymerase was activated. Furthermore, the N-acetyl-L-cysteine
antioxidant effectively prevented costunolide-induced cytotoxicity. These results suggested that costunolide-induced cell death is
mediated by reactive oxygen species (Park HJ et al., 2001). Other
results indicate that costunolide-induced c-Jun N-terminal kinase
(JNK) activation acts downstream of ROS but upstream of Bcl-2,
and suggest that ROS-mediated JNK activation plays a key role in
costunolide-induced apoptosis. Moreover, the administration of
costunolide (i.p. once a day for 7 d) significantly suppressed tumor
growth and increased survival in 3LLLewis lung carcinoma-bearing
model (Choi and Lee, 2009).
Costunolide (1), isolated from the stem bark of Magnolia sieboldii, demonstrated a significant inhibition upon the farnesylation
process of human lamin-B by farnesyl-proteintransferase (FPTase),
in a dose dependent manner in vitro (IC50 value was calculated as
20 lM). It was also found to exhibit an inhibition upon the proliferation of human tumor cell cultures, i.e., A549 (non small cell
lung), SK-OV-3 (ovary), SK-MEL-2 (melanoma), XF498 (central
nerve system) and HCT-15 (colon), in vitro (Park SH et al., 2001).
Costunolide (1) also inhibits the killing activity of cytotoxic T lymphocytes through preventing the increase in tyrosine phosphorylation in response to the crosslinking of T-cell receptors (Taniguchi
et al., 1995).
Costunolide (1) demonstrated inhibitory effect on the protein
and mRNA expression of interleukin-1 b (IL-1 b) in LPS-stimulated
RAW 264.7 cells. Costunolide was also shown to suppress the transcriptional activity of the IL-1 b promoter. Moreover, costunolide
inhibited the activity of AP-1 transcription factor, and the phosphorylation of MAPKs, including SAPK/JNK and p38 MAP kinase.
The inhibitory effect of costunolide on AP-1 activity was also confirmed by an electrophoretic mobility shift assay. These results
demonstrated that costunolide inhibits IL-1 b gene expression by
Please cite this article in press as: Bruno, M., et al. Sesquiterpenoids in subtribe Centaureinae (Cass.) Dumort (tribe Cardueae, Asteraceae): Distribution, 13C
NMR spectral data and biological properties. Phytochemistry (2013), http://dx.doi.org/10.1016/j.phytochem.2013.07.002
M. Bruno et al. / Phytochemistry xxx (2013) xxx–xxx
blocking the activation of MAPKs and DNA binding of AP-1 in LPSstimulated RAW 264.7 cells (Kang et al., 2004).
It has been also suggested that costunolide (1) induces apoptosis in human promonocytic leukemia U937 cells by depleting the
intracellular thiols. Costunolide treatment rapidly depleted the
intracellular reduced glutathione (GSH) and protein thiols, and this
preceded the occurrence of apoptosis. Pretreatment with sulfhydryl compounds such as GSH, N-acetyl-L-cysteine, dithiothreitol
and 2-mercaptoethanol almost completely blocked the costunolide-induced apoptosis, highlighting the significance of the intracellular thiol level in the process. Furthermore, overexpression of
Bcl-2 also significantly attenuated the effects of costunolide. The
apoptosis-inducing activity of costunolide is likely to depend on
the exomethylene moiety because derivatives, in which this group
was reduced, such as dihydrocostunolide and saussurea lactone,
did not deplete the cellular thiols and showed no apoptotic activity. In this study it has been demonstrated that the costunolide-induced apoptosis depends on intracellular thiols contents, which
are modulated by Bcl-2 (Choi et al., 2002a). Other studies were carried out on the induction mechanism of apoptosis by costunolide
in a human B cell leukemia NALM-6 cell culture system and the
data suggested that one of the costunolide-induced apoptotic
mechanisms is that the receptor-mediated pathway precedes the
mitochondria-dependent pathway, caused by the inhibition of telomerase activity via suppression of telomerase reverse transcriptase (hTERT) in NALM-6 cells (Kanno et al., 2008). Also, in the
case of MCF-7 and MDA-MB-231 cells, their growth inhibition
seem to be mediated at least in part by a significant reduction in
telomerase activity (Choi et al., 2005).
In the cell adhesion inhibitory activity test against B16-F1
mouse melanoma cell, costunolide (1) showed significant activities, with IC50 of 0.9 lg/mL. In the cytotoxicity test against several
human tumor cells, costunolide had an IC50 values of below 0.3 lg/
mL against all the tested cell lines except for UACC62. It exhibited a
stronger activity against HCT15 and UO-31 cell lines than a positive control, adriamycin (Jang et al., 1998b).
Costunolide (1) showed effective antiproliferative activity
against hormone dependent (LNCaP) and independent (PC-3 and
DU-145) prostate cancer cells (ATCC) by SRB assay, clonogenic test
and flow cytometric analalysis of carboxyfluorescein succinimidyl
ester labeling. In PC-3 cells, data showed that costunolide induced
a rapid overload of nuclear Ca2+, DNA damage response and ATR
phosphorylation (Hsu et al., 2011). It also had cytotoxic properties
against MCF-7, NCI-H460, and SF-268 cancer cell lines in vitro
(Chang et al., 2010), P-388, L-1210 leukemia and SNU-5 stomach
cancer cells (Kim et al., 1999) and against human A549, SK-OV-3,
SK-MEL-2, and HCT15 tumor cells (Park et al., 2010). Costunolide
(1) and the guainolide zaluzanin D (147) displayed strong growth
inhibitory effect against human promyelotic leukemia HL-60 cells
by induction of chromatin condensation in the HL-60 cells (Hibasami et al., 2003).
Costunolide (1) has been reported to exhibit potent chemopreventive effects on carcinogenesis. Modifying effects of costunolide
on intestinal carcinogenesis were examined in a rat model using
azoxymethane (AOM). The results suggest that the natural sesquiterpene could be a promising chemopreventive agent for human
intestinal neoplasia (Mori et al., 1994). Effects of costunolide on
cellular activation induced by a tumor-promoting phorbol ester
12-O-tetradecanoylphorbol-13-acetate (TPA) were investigated:
iNOS promoter-dependent reporter gene activity was significantly
increased by TPA, and the TPA-induced increase of the reporter
gene activity was efficiently reduced by costunolide, with an IC50
of approximatively 2 lM (Fukuda et al., 2001).
It was found that costunolide (1) selectively inhibits angiogenic
factors including basic fibroblast growth factor (bFGF) and vascular
endothelial growth factor (VEGF)-induced endothelial cells prolif-
63
eration and migration. From these results, it has been suggested
that costunolide would inhibit angiogenesis by blockade of angiogenic factors signaling pathway (Jeong et al., 2001, 2002).
Costunolide (1) could reduce the viability and arrest cell cycling
at mitosis in hepatoma cells. Logical exploration of this mitosisarresting activity for cancer therapeutics shows costunolide enhanced the killing effect of radiotherapy against human hepatocellular carcinoma (HCC) cells (Liu et al., 2011).
Investigations on the effect of costunolide (1) on cellular differentiation in the human promyelocytic leukemia HL-60 cell culture
system were carried out. Costunolide markedly increased the degree of HL-60 leukemia cell differentiation when simultaneously
combined with 5 nM 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3).
The results indicate that PKC, PI3-K, ERK and NF-jB may be involved in 1,25-(OH)2D3-mediated cell differentiation enhanced
by costunolide (Choi et al., 2002b; Kim et al., 2002).
Investigations of the anticancer effect of dehydrocostus lactone
(142) on human breast cancer cells (MCF7) (Kuo et al., 2009), human ovarian cancer cells (SK-OV-3) (Choi and Ahn, 2009), human
prostate cancer cells (DU145) (Kim et al., 2008), human non-small
cell lung cancer cell lines (A549, NCI-H460 and NCI-H520) (Hung
et al., 2010), HeLa, T-98, HLE and HMV-1 cells (Chen et al., 2011)
and HepG2 and PLC/PRF/5 cells (hepatocellular carcinoma) (Hsu
YL et al., 2009) were carried out. Compound 142 was shown to inhibit cell proliferation by inducing cells to undergo cell cycle arrest
and apoptosis.
Dehydrocostus lactone (142) inhibited the proliferation of
human lung cancer A549 cells in a time- and dose-dependent
manner. The cytometric analysis showed that the A549 cells were
arrested at the sub-G1 phase by the treatment of dehydrocostus lactone. The evidence of the activation of caspase-9 and -3 verified that
the death of A549 cells was through the apoptosis pathway. Dehydrocostus lactone also exhibited strong cytotoxicity on MDA-MB-231
(breast cancer) and HepG2 (hepatoma) cells (Hsu HF et al., 2009).
Dehydrocostus lactone (142), isolated from the medicinal plant,
Saussurea lappa, inhibited the production of NO in lipopolysaccharide (LPS)-activated RAW 264.7 cells by suppressing inducible NO
synthase enzyme expression (Lee et al., 1999).
The anti-proliferative activity of dehydrocostus lactone (142)
was investigated in human breast cancer (MDA-MB-231, MDAMB-453 and SK-BR-3) and ovarian cancer (SK-OV-3 and OVCAR3)
cell lines using the MTT assay. In the cells, exposure to dehydrocostus lactone resulted in a dose-dependent decline in cell proliferation. The IC50 value was found to be 21.5, 43.2, 25.6, 15.9 and
10.8 lM in MDA-MB-231, MDA-MB-453, SK-BR-3, SK-OV-3 and
OVCAR3 cells, respectively. Dehydrocostus lactone exerted its antiproliferative effects by inducing cell cycle arrest and apoptosis. Cell
cycle distribution and apoptosis were analyzed using flow cytometry in cell lines exposed to 10 lM dehydrocostus lactone for 48 h
(Choi and Kim, 2010).
It was demonstrated that dehydrocostus lactone (142), the major sesquiterpene lactone isolated from the roots of Saussurea lappa, inhibits NF-jB activation by preventing TNF-a-induced
degradation and phosphorylation of its inhibitory protein I-jBa
in human leukemia HL-60 cells and that 142 renders HL-60 cells
susceptible to TNF-a-induced apoptosis by enhancing caspase-8
and caspase-3 activities (Oh et al., 2004).
Costunolide (1) and dehydrocostus lactone (142) both showed
strong suppressive effect on the expression of the hepatitis B surface antigen (HBsAg) in human hepatoma Hep3B cells, but had little effect on the viability of the cells. Both costunolide and
dehydrocostus lactone suppressed the HBsAg production by Hep3B
cells in a dose-dependent manner with IC50 of 1.0 and 2.0 lM,
respectively (Chen et al., 1995).
Dehydrocostus lactone (142) and costunolide (1) exhibited potent dose- and time-dependent cytotoxicity with CD50 values in
Please cite this article in press as: Bruno, M., et al. Sesquiterpenoids in subtribe Centaureinae (Cass.) Dumort (tribe Cardueae, Asteraceae): Distribution, 13C
NMR spectral data and biological properties. Phytochemistry (2013), http://dx.doi.org/10.1016/j.phytochem.2013.07.002
64
M. Bruno et al. / Phytochemistry xxx (2013) xxx–xxx
the range 1.6–3.5 lg/mL against HepG2, OVCAR-3 and HeLa
human cancer cell lines whereas zaluzanin C (147), santamarin
(99) and reynosin (100) which are less lipophilic due to the presence of an hydroxyl group, showed lower cytotoxicity (Sun et al.,
2003).
Costunolide (1), santamarine (99), reynosin (100) obtained
through bioactivity-directed isolation from a methanol extract of
the fruits of Laurus nobilis were found to be highly cytotoxic against
the A2780 ovarian cancer cell line (Barla et al., 2007). Furthermore,
cytotoxicity testing of the sesquiterpene lactone reynosin (100)
against the KB cancer cell line (ATCC CCL17) revealed IC50 values
of 2.7 lg/mL (Hilmi et al., 2003).
Dehydrocostus lactone (142), santamarine (99) and b-cyclocostunolide (98) showed effects on inhibited proliferation of human
stomach cancer cells MGC-803, human pharyngeal cancer cells
KB, human lung cancer cells NCI-H460, and human colon cancer
cells HT-29 cultured for 72 h (IC50 < 10.0 mg/mL), and had weak effect on inhibiting proliferation of human liver cancer cells HepG-2
cultured for 72 h (IC50 = 16.3, 48.7, and 16.1 mg/mL, respectively)
(Tang et al., 2010).
Cyathocline purpurea has been traditionally used to treat various
diseases including cancers for many years and santamarine (99),
one of its main constituents, inhibited the growth of L1210 murine
leukemia, CCRF-CEM human leukemia, KB human nasopharyngeal
carcinoma, LS174T human colon adenocarcinoma and MCF 7 human breast adenocarcinoma cells in vitro, with IC50 in the range
of 0.16–1.3 lg/mL. In the L1210 model, santamarine inhibited cell
growth, colony formation and [3H]-thymidine incorporation in
time- and concentration-dependent manners. The mechanism of
the cytotoxicity of santamarine towards L1210 cells could be related to alkylation of the sulfhydryl enzymes involved in nucleic
acids and protein synthesis, as previously found for other SLs with
the a-methylene-c-lactone moiety. Santamarine (99) induced
apoptosis of L1210 cells via activation of caspase 3 (Ma et al.,
2009) and had moderate inhibitory effect on topoisomerases
(Zhang et al., 2007). Santamarine (99) has been used as cytotoxic
anticancer agent that is selective to mouse leucocythemia cell
(L1210), human leucocythemia cell (CCRF-CEM), human nasopharyngeal carcinoma cell (KB), human mammary gland cancer cell
(MCF-7), and human colon cancer cell (LS174T). The IC50 is 0.41,
0.59, 0.16, 0.92 and 0.53 lg/mL to the above tumor cells respectively, and the anticancer activity is in direct proportion to santamarine concentration and action time. The anticancer mechanism
of santamarine relates to the inhibition of tubulin. Santamarine
leads to tumor cell necrosis, not apoptosis (Li, 2005). Santamarin
(99) and reynosin (100) have been reported to exhibit cytotoxic
activity against the human lung carcinoma cell line GLC4 and the
colorectal cancer cell line COLO 320 with IC50 in the range
7.4–10.7 lM (Goren et al., 1996).
4.5. Antiviral
Chlorohyssopifol A (224) and rhaposerin (248) suppressed
reproduction of influenza virus by more than 50% at 5 lM concentration. Compound 224 decreased the infecting ability of virus of
Newcastle disease (Berdin et al., 1999).
Antiviral properties of 13-acetyl solstitialin A (183), chlorojanerin (219) and centaurepensin (224) were screened against Herpes
simplex type-1 (representative of DNA virus) and Parainfluenza
(representative of RNA virus) were employed for the determination
of antiviral activity. 13-acetyl solstitialin A (183) had significant
activity against DNA virus over a wide range of concentration
(16 lg/mL–6 10 5 lg/mL) (Gürbuz et al., 2006;Ozcelik et al.,
2009).
4.6. Effects on insects
Grosheimin (264), and repin (209), administered in 0.1 mg/g
doses to Tenebrio molitor larvae, inhibited its growth and showed
antifeedant activity. Growth inhibition was due not only to reduced food intake but also to decreased absorption of digested food
constituents and metabolic disorders (Rosinski et al., 1988). Also
stizolin (27), 9a-hydroxypartenolide (28), stizolicin (32), aguerin
B (160) and chlorojanerin (219) showed good antifeedant
properties against Sitophilus granaries, Trogoderma granarium and
Tribolium confusum, while janerin (208) and cynaropicrin (162)
inhibited feeding of the latter species only (Cis et al., 2006;Bloszyk,
1988).
Cynaropicrin (162) was proved to be a potent feeding deterrent
on testing against 4th instar larvae of Bihar hairy caterpillar, Diacrisia obliqua and the eri-silkworm Philosamia ricini (Bhattacharyya
et al., 1996).
The antifeedant activity of compounds, 162, 208, 209, 212,
219,222,224, 240, 243, 244 and 246 were tested against larvae of
Spodoptera littoralis. The chlorine-containing guaianes, 217, 219
and 246 showed significant activity at 100 ppm (Rosselli et al.,
2006a).
Shiromool (52) showed significant antifeedant activity against
the larvae of S. littoralis whereas compound 51 was inactive (Barrero et al., 1999).
Cnicin (19) exhibited significant mortality against the Formosan
subterranean termite, Coptotermes formosanus, one of the most
devastating termite pests (Meepagala et al., 2006) and was shown
to be a disrupter of insect metamorphosis and modifier of reduced
glutathione synthesis (Maymò et al., 1999). Furthermore, the effects of cnicin (19) on the ovopositional response and larval development of generalist and specialist insect herbivores were
investigated as well as the toxicity on the larvae of S. littoralis (Landau et al., 1994).
Compounds 64 and 83 produce altering effects on the metamorphosis of the grasshopper Locusta migratoria when topically applied to the nymphs (Castillo et al., 1998).
Several SLs were examined for their nematocidal activity
against root-knot nematode as a function of their structure. Maximum nematocidal activity was associated with an a-methylene-clactone moiety, e.g., alantolactone (121) (97% mortality) (Mahajan
et al., 1986).
HPLC-bioactivity-guided fractionations led to the isolation of
costic acid (124) showing repellent activity against subterranean
termite C. formosanus (Watanabe et al., 2005). Furthermore costic
acid (124) had selective cytotoxic effects toward insect-derived
Sf9 cells (Gonzalez-Coloma et al., 2005).
The larvicidal activities of alantolactone (121), isolated from the
roots of I. helenium, against 3rd and 4th instars of Aedes albopictus
(Diptera: Culicidae) and Paratanytarsus grimmii (Diptera: Chironomidae), were examined. It showed LC50 values of 2.7 lg/mL for
A. albopictus and 5.1 lg/mL for P. grimmii, respectively (Konishi
et al., 2008). It also had larvicidal activity against Aedes aegypti
(Cantrell et al., 2010) and insect feeding deterrent properties
(Picman et al., 1978).
Also dehydrocostus lactone (142), isolated from the dichloromethane extract of the Portuguese liverwort T. lorbeeriana,
presented larvicidal activity against A. aegypti (Gonzalez-Coloma
et al., 2005).
Costunolide (1), isolated from the fruits of Magnolia salicifolia
exhibited 100% mortality on 4th instar A. aegypti at 15 ppm, in
24 h (Kelm et al., 1997).
Studies showed the insect repellent activity found in Saussurea
lappa rhizomes to be due to dehydrocostus lactone (142) (Malik
and Naqvi, 1984).
Please cite this article in press as: Bruno, M., et al. Sesquiterpenoids in subtribe Centaureinae (Cass.) Dumort (tribe Cardueae, Asteraceae): Distribution, 13C
NMR spectral data and biological properties. Phytochemistry (2013), http://dx.doi.org/10.1016/j.phytochem.2013.07.002
M. Bruno et al. / Phytochemistry xxx (2013) xxx–xxx
4.7. Effects on plants
The SLs repin (209), acroptilin (212), solstitiolide (222), and
centaurepensin (224) caused increased lettuce root elongation at
10 ppm and inhibited it at higher concentrations (Stevens and
Merrill, 1985). Cnicin (19) and onopordopicrin (8) drastically reduced the germination of lettuce and honey weed. Furthermore
cnicin (19) at 0.1 mg/g concentration selectively inhibited some
soil microorganisms (Cabral et al., 2008) and was shown to have
germination and growth inhibitor properties (Kelsey and Locken,
1987; Locken and Kelsey, 1987). Stizolin (27) has been tested on
inhibition of seed germination of wheat and showed an excellent
phytotoxic activity (Starykh and Konovalov, 1997). Costunolide
(1) and dehydrocostus lactone (142) caused inhibition of radicle
growth of seedlings of Amaranthus hypochondriacus (Mata et al.,
2002). A structure–activity study to evaluate the effect of the
trans,trans-germacranolide sesquiterpene lactone, costunolide (1),
and some derivatives (in a range of 100–0.001 lM) on the growth
and germination of several mono- and dicotyledon target species,
was accomplished. These compounds appeared to have a selective
effect on the radicle growth of monocotyledons at levels comparable to those of Logran (Macias et al., 1999a). Zaluzanin C (147) was
shown to inhibit root and shoot growth in lettuce, tomatoes and
cress (Macias et al., 1999b, 2010).
4.8. Other activities
In the nitric oxide release inhibitory experiments, costunolide
(1) exhibited strong inhibition with an IC50 value of 0.2 lg/mL
(0.86 lM). In the ACAT (acyl CoA: cholesterol acyltransferase)
inhibitory assay, costunolide exhibited strong inhibition, with an
IC50 value of 17 lg/mL (73.3 lM) (Jang et al., 1999).
A study demonstrated that dehydrocostus lactone (142) can
protect osteoblasts against H2O2-induced cellular dysfunction.
The results also suggest that 142 may be valuable as a protective
agent against oxidative damage in osteoblasts (Choi et al., 2009)
and, furthermore, it protects osteoblastic MC3T3-E1 cells from
antimycin A induced cell damage through the improved mitochondrial function (Choi, 2011). The effect of costunolide (1) on the
function of osteoblastic MC3T3-E1 cells was studied. Costunolide
significantly increased the growth of MC3T3-E1 cells and caused
a significant elevation of alkyl phosphatase (ALP) activity, collagen
content, and mineralization in the cells (P < 0.05). These data indicate that the enhancement of osteoblast function by costunolide
may result in the prevention for osteoporosis (Lee and Choi, 2011).
The molecular mechanism of inhibitory action of dehydrocostus
lactone (142) and costunolide (1) towards the activation of signal
transducer and activator of transcription 3 (STAT3) was studied.
In human THP-1 cell line, they inhibit IL-6-elicited tyrosine phosphorylation of STAT3 and its DNA binding activity with EC50 of
10 lM with concomitant down-regulation of the phosphorylation
of the tyrosine Janus kinases JAK1, JAK2 and Tyk2. Furthermore,
these compounds that contain an a b-unsaturated carbonyl moiety and function as potent Michael reaction acceptor, induced a rapid drop in intracellular glutathione (GSH) concentration by direct
interaction with it, thereby triggering S-glutathionylation of
STAT3. It was concluded that SLs 142 and 1 are able to induce redox-dependent post-translational modification of cysteine residues of STAT3 protein in order to regulate its function (Butturini
et al., 2011).
Costunolide (1) and dehydrocostus lactone (142), the active
principle from the leaves of Laurus nobilis, were shown to inhibit
selectively ethanol absorption rather than glucose absorption and
to have a gastroprotective effect on acidified ethanol-induced gastric mucosal (Yoshikawa et al., 2000) lesions in rats (Matsuda et al.,
2000b). The inhibitory mechanism of costunolide was investigated
65
(Matsuda et al., 2002). In other studies through bioassay-guided
separation from methanolic extract of the leaves of Laurus nobilis,
costunolide (1), dehydrocostus lactone (142), and santamarine
(99) were isolated as the active constituents that inhibited the elevation of blood ethanol level in ethanol-loaded rat; the a-methylene-c-butyrolactone moiety was found to be essential for the
preventive effect on ethanol absorption (Matsuda et al., 1999).
Costunolide (1) and dehydrocostus lactone (142) showed strong
cholagogic effect (Wang et al., 2001).
It has been shown that artichoke leaf extract is effective against
acute gastritis and its beneficial effect is due to that of cynaropicrin
(162) (Ishida et al., 2010).
A study of the cytoprotective activity of several guaianolides
was undertaken. Ludartin (262) was found to exhibit good protection (Giordano et al., 1990). The structural activity relationship of
the antiulcerogenic activity and the mechanism of action were
investigated. It has been ascertained that a sterically unhindered
Michael acceptor is an essential requirement for the activity, interacting with the thiol containing compounds of the gastric mucosa
(Giordano et al., 1992).
The main components of C. solstitialis ssp. solstitialis responsible
for its significant anti-ulcerogenic activity were determined as
solstitialin A (181), 13-acetyl solstitialin A (183) and chlorojanerin
(219) (Yesilada et al., 2004;Gürbüz and Yesilada, 2007).
Saussurea root has been used in Oriental medicine as sedative,
as well as in incense. Dehydrocostus lactone (142) and costunolide
(1) were isolated from this root and found to have sedative and
analgesic effects on the central nervous system. The sedative effects of these two compounds were found to be caused by antidopaminergic and partly anti-serotonergic effects (Okukawa
et al., 2000): they also increased hexobarbital sleeping time and
decreased body temperature, nociception, and spontaneous locomotor activity (Okugawa et al., 1996).
The analgesic effect of 8a-(30 -hydroxy-40 -acetoxy-20 -methylene-butanoyloxy)-4-epi-sonchucarpolide (111), isolated from C.
grisebachi, and of 8a-O-(40 -hydroxy-20 -methylenebutanoyloxy)11b,13-dihydrosonchucarpolide (118), isolated from C. pullata,
was studied in mice. The results showed significant decreasing in
pain at 30 min post treatment with a dose of 10 mg/kg (Djeddi
et al., 2008c). Solstitialin A (181) and 13-acetyl solstitialin A
(183) were defined as the active components responsible of the
antinociceptive and antipyretic properties C. solstitialis and C. depressa (Akkol et al., 2009).
It has been demonstrated that the a-methylene-c-butyrolactone structural unit of dehydrocostus lactone (142) is the moiety
responsible for increasing cellular resistance to oxidant injury in
HepG2 cells, presumably through Nrf2/ARE-dependent HO-1
expression (Jeong et al., 2007).
The hexane fraction of I. helenium showed the potential to induce detoxifying enzymes such as quinine reductase (QR) and
glutathione S-transferase in a dose-dependent manner. Its potential to induce the reported activity, suggested an antioxidant response element-mediated mechanism of action in the induction
of phase II detoxifying enzymes. Alantolactone (121) isolated
from this fraction significantly induced QR activity in both
Hepa1c1c7 and BPRc1 cells (Im et al., 2007) and was shown to
be a more effective antioxidant than a-tocopherol or ubiquinone
(Mir-Babaev and Sereda, 1987).
Alantolactone (121) caused a dose-dependent induction of antioxidant enzymes including QR, GST, c-glutamylcysteine synthase,
glutathione reductase, and heme oxygenase 1 in hepa1c1c7 mouse
hepatoma cells. The compound increased the luciferase activity of
HepG2–19 cells, transfectants carrying antioxidant response element (ARE)-luciferase gene, in a dose-dependent manner, suggesting ARE-mediated transcriptional activation of antioxidant
enzymes. Alantolactone also stimulated the nuclear accumulation
Please cite this article in press as: Bruno, M., et al. Sesquiterpenoids in subtribe Centaureinae (Cass.) Dumort (tribe Cardueae, Asteraceae): Distribution, 13C
NMR spectral data and biological properties. Phytochemistry (2013), http://dx.doi.org/10.1016/j.phytochem.2013.07.002
66
M. Bruno et al. / Phytochemistry xxx (2013) xxx–xxx
of Nrf2 that was inhibited by phosphatidylinositol 3-kinase (PI3K)
inhibitors. In conclusion, alantolactone appears to induce detoxifying enzymes via activation of PI3K and JNK signaling pathways,
leading to translocation of Nrf2, and subsequent interaction between Nrf2 and ARE in the encoding genes (Seo et al., 2008).
Grosheimin (264), isolated from the medicinal plants of Youngia
japonica, exhibited strong antiallergic and antioxidant activities
(Yae et al., 2009).
Costunolide (1) and reynosin (100), isolated from Saussureae
Radix, showed potent inhibitory effects on the IBMX-induced
melanogenesis, in dose-dependent manners, with IC50 values of 3
and 2.5 lg/mL, respectively (Choi et al., 2008). Costunolide (1)
inhibited contractions of the aorta induced by KCl but exerted less
effect on those induced by norepinephrine, indicating the possible
Ca antagonistic action of costunolide. Dehydrocostus lactone (142)
caused similar inhibitor effects but its specificity of KCl-induced
contraction was less than costunolide (Shoji et al., 1984).
The oxygen functional groups at the 3- and 8-positions and exomethylene moiety in a-methylene-c-butyrolactone ring were
found to be essential for the anti-hyperlipidemic activity of guaiane-type sesquiterpene. In fact cynaropicrin (162), aguerin B
(160) and grosheimin (264) significantly suppressed serum TG elevation at 50 and 100 mg/kg during the early stage (2 h after olive
oil administration), whereas dehydrocostus lactone (142) and
11b, 13-dihydro-deacylcynaropicrin (190) had a weaker activity
(Shimoda et al., 2003).
In vitro protein synthesis was blocked by zaluzanin C (147) and
the study of the effects of the drug on resolved model systems indicates that it inhibits enzymic translocation of peptidyl-tRNA specifically (Santamaria et al., 1984). The Acyl-CoA cholesterol
acyltransferase (ACAT), diacylglycerol acyltransferase (DGAT) and
farnesyl-protein transferase (FPTase) inhibitory effects of the roots
of Ixeris dentata forma albida were investigated and one of the active compounds was identified as zaluzanin C (147) (Bang et al.,
2004). The inhibition of ATP synthesis, proton uptake, and electron
transport (basal, phosphorylating, and uncoupled) from water to
methylviologen by zaluzanin C (147) indicates that it acts as an
electron transport inhibitor. The studies concluded that the site
of inhibition by zaluzanin C is located at the oxygen evolution level
(Lotina-Hennsen et al., 1992).
An inhibitor of CINC-1 (cytokine-induced neutrophil chemoattractant-1) induction in LPS-stimulated rat kidney epithelioid
NRK-52E cells was purified from the roots of Sassurea lappa, a herbal medicine used in Korean traditional prescriptions for gastric
intestinal diseases by a variety of column chromatography procedures. The inhibitor was identified as reynosin (100). It exhibited
a dose-dependent inhibition on CINC-1 induction in LPS-stimulated NRK-52E cells, where 50% of inhibitory effect was shown at
the concentration of about 1 lM (Jung et al., 1998). Furthermore,
reynosin (100) displayed considerable inhibition against platelet
aggregation induced by AA, ADP, or PAF (Wang et al., 2000).
A study describing the antispasmodic activity of some fractions
and cynaropicrin (162), a sesquiterpene lactone from Cynara
scolymus, cultivated in Brazil, against guinea-pig ileum contracted
by acetylcholine was carried out. The dichloromethane fraction
showed the most promising biological effects, with an IC50 of
0.93 (0.49–1.77) lg/mL. Its main active component, the sesquiterpene lactone cynaropicrin, exhibited potent activity, with IC50 of
0.065 (0.049–0.086) lg/mL, being about 14-fold more active than
dichloromethane fraction and having similar potency to that of
papaverine, a well-known antispasmodic agent (Emendoerfer
et al., 2005).
A characteristic smooth muscle inhibitory profile is demonstrated by the a-methylenebutyrolactone cynaropicrin (162), but
not by a compound lacking this functional group (solstitialin
13-acetate, 183) (Hay et al., 1994).
Repin (209), on intraperitoneal injection, produces a dosedependent and highly significant hypothermia in naive rats (Akbar
et al., 1995).
Several SLs isolated from different Asteraceae species from
north-western Argentina were investigated for their inhibitory action on the estrogen biosynthesis. Ludartin (262) was found to inhibit the aromatase enzyme activity in human placental
microsomes and it was competitive inhibitor with an apparent Ki
of 23 lM (Blanco et al., 1997).
Compounds 220 and 221 displayed promising inhibitory potential against enzyme urease in a concentration-dependent fashion
(Khan et al., 2004a).
Compounds 190, 198, 217, 219, 236 and 240 showed inhibitory
potential against butyrylcholinoesterase, the best one being
chlorojanerin (219) with IC50 values of 15 lg/mL (Khan et al.,
2005a).
5. Conclusions
This subtribe Centaureinae appears taxonomically very
complex. It is worth to keep in mind that, in the numerous papers
reviewed, the correct botanic identification plays a pivotal role.
Moreover, the correct assessment of the taxa in their sections is
a further problem in order to draw any chemotaxonomic
classification.
The elaboration of the collected data allows to define groups of
taxa with a consistent chemical composition reflecting a botanic
relationship, i.e. Psephellus and Acrolophus sections. Other
similarities or differences can be found, i.e. Cheirolophus intybaceus
showing a complete different profile with respect to the other
species of genus Cheirolophus or C. calcitrapa, C. incana, C. salonitana
and C. solstitialis that have a very different composition depending
on the collection place. Clearly, all the information arising from
the statistical approach of the qualitative content of sesquiterpenes in the taxa, both single product and structural similarity products methods, should be evaluated for any botanical consistency.
As it is possible to observe, the main biological properties
ascribed to sesquiterpenes are the antibacterial, anti-inflammatory
and antitumor activities. In this context, a lot of publications
regarding custonolide (1) and cynaropicrin (162), have shown a
high potential towards these activities.
Acknowledgment
This work was supported by Italian Government fund MIUR
PRIN 2009 ‘‘Composti naturali da piante mediterranee e loro derivati sintetici con attivita’ antitumorale’’.
Appendix A. Supplementary data
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.phytochem.2013.
07.002.
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President of the Italian Republic appointed him as ‘‘Commendatore dell’Ordine al
Merito della Repubblica Italiana’’ for his contributions to the scientific research. At
the present he is President of the Societá Chimica Italiana – Sez. Sicilia.
Svetlana Temelkova Bancheva is associate professor of
botany at the Institute of Biodiversity and Ecosystem
Research, Bulgarian Academy of Sciences. She is currently Head of the Department of Plant and Fungal
Diversity and Resources and Curator of the Herbarium
(SOM) of the Institute of Biodiversity and Ecosystem
Research at Bulgarian Academy of Sciences. Her interests are focused on the taxonomy and biosystematics of
vascular plants, endemism, plant protection, protected
sites and chemotaxonomy. She is author of more than
66 scientific publications and member of the Managing
Committee of the Balkan alliance for Nature protection,
member of the Commission for Floristic Researches of OPTIMA, member of the
Bulgarian Society of Botany and member of the Society of the Bulgarian Scientists.
Sergio Rosselli is assistant professor of organic chemistry at the University of Palermo. His scientific interests
are mainly devoted to the chemistry of secondary
metabolites from plants and their potential biological
applications. His expertise ranges from isolation and
purification to structural elucidation of natural products
with regard to NMR techniques; he is also interested in
the characterization of the essential oils, in chemical
modification of natural products and structure–activity
relationships. His scientific activity is demonstrated by
about 110 scientific publications.
Antonella Maggio is assistant professor of organic
chemistry at the University of Palermo. The scientific
activity of Dr. Maggio has always been focused on the
chemistry of natural substances. In particular she is
interested in the chemistry of the diterpenes and sesquiterpenes of plant origin, notably from the Mediterranean basin. The research work of Dr. Maggio has been
and is orientated specifically towards the study of
plants of the family Labiatae and Compositae for the
isolation of new natural products-type diterpene and
sesquiterpene. She is co-author of about 60 scientific
publications.
Maurizio Bruno is full professor of organic chemistry at
the University of Palermo. He studied at the Florida
State University with Prof. Werner Herz and at the
Imperial College, London, with Prof. Steven Ley. He
works in natural organic products chemistry on natural
and semi-synthetic terpenoids with antifeedant activity.
He is interested in sesquiterpenes from Compositae, in
natural and semi-synthetic compounds with anti-HIV
and cytotoxic activity and in the extraction and analysis
of essential oils with antibacterial and antifungal
properties. He is author of more than 240 papers on
international journals. He was coordinator of joint programs CNR-CSIC (Spain) and CNR-BAS (Bulgaria). From 2002 he has been included
in the ISI list as one of the most cited Italian researchers in the world. In 2005 the
Please cite this article in press as: Bruno, M., et al. Sesquiterpenoids in subtribe Centaureinae (Cass.) Dumort (tribe Cardueae, Asteraceae): Distribution, 13C
NMR spectral data and biological properties. Phytochemistry (2013), http://dx.doi.org/10.1016/j.phytochem.2013.07.002