J. Nat. Prod. 1998, 61, 1509-1512
1509
Cytotoxic Geranyl Stilbenes from Macaranga schweinfurthii
John A. Beutler,† Robert H. Shoemaker, Tanya Johnson, and Michael R. Boyd*
Laboratory of Drug Discovery Research and Development, Developmental Therapeutics Program,
Division of Cancer Treatment and Diagnosis, National Cancer Institute-Frederick Cancer Research and
Development Center, Frederick, Maryland 21702-1201
Received May 18, 1998
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Publication Date (Web): October 24, 1998 | doi: 10.1021/np980208m
Three novel geranyl stilbenes, schweinfurthins A, B, and C (1, 2, and 3), were isolated from the
Cameroonian plant Macaranga schweinfurthii (Euphorbiaceae) and their structures determined by NMR
and mass spectral methods. The cytotoxicity profile of the schweinfurthins tested in the NCI 60-cell
screen was similar to that of the stelletins and cephalostatins, suggesting that these structurally diverse
natural products may share similar mechanisms of cytotoxicity.
The genus Macaranga is one of the largest genera of the
Euphorbiaceae, with approximately 300 species.1 Previously reported compounds from the genus include a prenyl
stilbene, vedelianin2 and a geranyl flavonol3 from M.
vedeliana, antibacterial prenylated flavanones from M.
pleiostemona,4 chromenoflavones from M. indica,5 and a
diterpene from M. tanarius.6 A number of species of
Macaranga are substantial sources of hydrolyzable tannins.7 No phytochemistry has been previously reported on
M. schweinfurthii, and none of the above-cited compounds
is documented to be cytotoxic. Our preliminary testing of
Macaranga extracts available from the NCI repository
found 11 samples from eight species of Macaranga, including M. schweinfurthii, to be devoid of phorbol ester bioactivity.8,9
For the present study we selected an organic extract of
M. schweinfurthii Pax based upon its prominent cytotoxicity toward several human tumor cell lines in the NCI
panel,10,11 notably the CNS tumor-derived lines SF-295 and
SF-539. Here we describe the bioassay-guided isolation
and structure elucidation of the compounds responsible for
this cytotoxicity.
Results and Discussion
Batch elution from diol bonded-phase media, Sephadex
LH-20 permeation, C-18 vacuum liquid chromatography,
and C-18 HPLC led to compounds 1 and 2 as the major
cytotoxic constituents. Compound 3 was found as an
inactive major congener.
Compound 1 was an optically active yellow glass [R]D
+51.8° with a molecular formula of C34H44O6, as determined by HRFABMS. The UV maximum at 331 nm was
consistent with a stilbene such as vedelianin,2 and the 1H
and 13C NMR spectra of 1 (Table 1) shared many features
with this compound. The molecular formula of compound
1 differed by C5H8 from vedelianin (4), consistent with the
presence of an additional prenyl group. HMQC and HMBC
spectra confirmed that the planar structure of 1 was
otherwise identical to vedelianin, and HMBC correlations
between a signal at δ 2.05 (H-6′′) and a methylene 13C
resonance at δ 40.9 (C-5′′), as well as δ 134.8 ppm (C-3′′),
established the point of substitution for the additional
prenyl group. The congruency of chemical shifts and scalar
couplings in the cyclohexyl ring and similar sign and
magnitude of optical rotations indicated that 1 possessed
the same relative stereochemistry as 4.
†
SAIC-Frederick, NCI-FCRDC, Frederick, MD 21702-1201.
Compound 2 had the formula C35H46O6 by HRFABMS,
differing from 1 by an additional CH2. This was also
evident in the 1H NMR (Table 2) by presence of a 3H singlet
at δ 3.83 and a 13C NMR resonance at δ 56.4. An HMBC
correlation from this methyl group to the resonance at δ
150.1 placed the methoxyl group at C-5, which was shifted
3 ppm compared to compound 1. Further HMBC correlations for 2 (data not shown) supported the assigned
structure.
Schweinfurthin C (3) had the molecular formula C34H44O4
by HRFABMS. The absence of 13C NMR resonances between 70 and 80 ppm (Table 3) indicated that this compound lacked the vicinal diol functionality of compounds 1
and 2. There were six methyl singlets in the 1H NMR
spectrum (from δ 1.55 to δ 1.75) and four vinyl triplets.
10.1021/np980208m This article not subject to U.S. Copyright. Published 1998 by the Am. Chem. Soc. and the Am. Soc. of Pharmacogn.
Published on Web 10/24/1998
1510 Journal of Natural Products, 1998, Vol. 61, No. 12
Table 1.
125 MHz)
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Publication Date (Web): October 24, 1998 | doi: 10.1021/np980208m
carbon
no.
1
2
3
4
4a
5
6
7
8
8a
9
9a
10a
11
12
13
1′
2′
3′
4′, 8′
5′, 7′
6′
1′′
2′′
3′′
4′′
5′′
6′′
7′′
8′′
9′′
10′′
MeO-5
13C
NMR Data for 1, 2, and 4 (δ in ppm, CD3OD,
13C
13C
shift 2,
DEPT
multiplicity
shift
1
39.1
78.8
71.7
44.6
78.2
147.0
111.1
130.8
120.5
124.2
23.9
48.8
137.6
16.3
29.4
22.0
128.7
127.4
141.9
105.7 × 2
157.2
115.9
23.2
124.6
134.9
13.5
40.9
27.8
125.6
131.9
17.7
25.8
39.1, s
78.7, d
71.7, d
44.7, t
78.0, s
150.1, s
108.3, d
130.6, s
121.7, d
124.3, s
23.9, t
48.6, d
137.5, s
16.2, q
29.3, q
21.9, q
128.5, d
127.6, d
143.3, s
105.8 × 2, d
157.2 × 2, s
115.9, s
23.2, t
124.5, d
134.8, s
16.5, q
40.9, t
27.7, t
125.5, d
131.9, s
17.7, q
25.8, q
56.4, q
13C
shift 44
39.0
78.7
71.7
44.5
78.0
146.8
111.0
130.7
120.5
124.1
23.8
48.6
137.6
16.2
29.3
22.0
128.8
127.3
141.8
105.9
157.1
115.9
23.3
124.5
131.3
25.9
17.9
HMQC to
1H for 2
3.30
4.14
2.34, 1.94
6.91
6.84
2.75
1.74
1.76
1.10
1.40
6.87
6.77
6.47
3.30
5.25
1.05
1.94
2.05
5.07
1.56
1.62
3.83
Table 2. 1H NMR of Schweinfurthin B (2) (CD3OD,
500 MHz)
proton no.
COSY to 1H
difference NOE to 1H
2
3
4
4a
5-MeO6
8
9
9a
11
12
13
1′
2′
4′, 8′
1′′
2′′
4′′
5′′
6′′
7′′
9′′
10′′
4.14
3.30, 2.34, 1.94
1.94
2.34
3.30, 2.34, 1.94
4.14, 1.94, 1.40
6.83
6.91
1.74
2.75
6.77
6.87
5.25
3.30
2.05
1.94
2.05, 1.56, 1.62
3.30, 1.94, 2.05
Beutler et al.
Table 3. Results of In Vitro Time-Course Experiments with
Schweinfurthins A (1) and B (2) in Sensitive (SF-295) and
Resistant (A549) Cell Linesa
compound
protocol
1h
1 h washout
48 h
a
1
A549
43
20
3.7
SF-295
47
0.06
<0.00001
2
A549
>100
80
7.1
SF-295
>100
2.9
0.009
Values are IC50 in µg/mL.
phenolic carbon resonances at δ 144.2 (C-1) and δ 146.1
(C-2), establishing this ring as a 3,5-disubstituted 1,2catechol.
The purified compounds were evaluated in an in vitro
time-course experiment using SF-295 and a resistant cell
line, A-549. A 1-h treatment with compounds 1 and 2 led
to negligible cytotoxicity, indicating that the compounds
were not cytotoxic through a rapid mechanism such as
membrane lysis. A 1-h treatment followed by compound
washout and evaluation at 48-h demonstrated a modest
differential cytotoxicity for each compound, while continuous 48 h treatment with the compounds generated a robust
differential (Table 3).
Compounds 1 and 2 were tested in the 60-cell line human
tumor cancer screen.10 Schweinfurthin A (1) showed a
mean panel GI50 of 0.36 µM, while schweinfurthin B (2)
was slightly less potent, giving a mean panel GI50 of 0.81
µM. The brain tumor (CNS) subpanel was the most
sensitive to both compounds, while the ovarian cancer cell
lines were uniformly resistant. The most sensitive cell line
was the CNS line SF-295, for which schweinfurthin A (1)
gave a GI50 of 11 nM and a TGI of 52 nM. Other sensitive
lines included leukemia (CEM, HL-60, MOLT-4, and RMPI8226) and lung (HOP-62), CNS (SF-539 and SNB-75), renal
(786-0, RXF-393, and UO-31), and breast (HS 578T)
cancers. The differential cytotoxicity profiles are further
documented in the Experimental Section.
The NCI 60-cell mean-graph cytotoxicity profiles showed
little or no resemblance to those of any of the profiles in
the NCI’s standard agents database.12 However, when
analyzed at the GI50 and TGI levels of response using the
Compare program,12,13 the schweinfurthins showed relatively high correlations to stellettin A14 (e.g., 0.75, 0.75)
and cephalostatin 115 (e.g., 0.59, 0.66). The cell lines
sensitive to these compounds differ substantially in many
known characteristics including in vitro doubling time,
DNA repair phenotype, and MDR status. No common
biochemical feature of these lines is apparent which could
explain their particular sensitivity to these compounds.
These results suggest that the schweinfurthins may
share with the stellettins and cephalostatins similar
mechanism(s) of cytotoxicity.
Experimental Section
1.62
These observations were accountable to a stilbene with two
geranyl chains and four phenolic groups. Although the
NMR data indicated that one side chain was attached in
the same fashion as in 1 and 2, the other geranyl group
was different. The second geranyl substituent was placed
by the HMBC correlations of the aromatic proton at δ 6.67
(H-5) to the methylene carbon resonance at δ 29.1 (C-7)
and the phenolic carbon at δ 144.2 (C-1). The aromatic
ortho-coupled proton (δ 6.81, H-3) was correlated to the
General Experimental Procedures. NMR spectra were
acquired on a Varian VXR-500 spectrometer with an inverse
detection probe. Optical rotations were obtained on a PerkinElmer model 204 polarimeter. UV spectra were acquired using
a Beckman DU640 spectrophotometer, while IR spectra were
obtained on a Perkin-Elmer Spectrum 2000 FT-IR spectrophotometer. FABMS were obtained on a JEOL SX102 mass
spectrometer operated at an accelerating voltage of 10 kV.
Samples were desorbed from a nitrobenzyl alcohol matrix
using 6 keV xenon atoms. Mass measurements in FAB were
performed at 10 000 resolution using electric field scans and
the matrix ions as the reference material.
Plant Material. Leaves of Macaranga schweinfurthii Pax
were collected by D. W. Thomas (Thomas 6771, voucher in
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Publication Date (Web): October 24, 1998 | doi: 10.1021/np980208m
Geranyl Stilbenes from Macaranga
Missouri Botanical Garden, collection Q66P364) in the vicinity
of Mundemba, Ndian Division, Korup National Park, Cameroon, in March 1987.
Cytotoxicity Bioassay. Two cell lines from the NCI CNS
screening panel (SF-295 and SF-539) were chosen for a twoday cytotoxicity assay16 to monitor fractionation.
Isolation. Ground, dry leaves (425 g) were extracted with
CH2Cl2-MeOH (1:1 v/v) and then MeOH; the solvent was
evaporated to yield 22.4 g of organic extract. Of this extract
5.0 g was coated on 25 g of diol media (YMC) and eluted with
500 mL each of hexane, CH2Cl2, EtOAc, Me2CO, and MeOH
in sequence. The EtOAc fraction (1.55 g) contained ca. 94%
of the cytotoxicity and was further fractionated by permeation
though Sephadex LH-20 using CH2Cl2-MeOH (1:1 v/v). The
fourth of five fractions collected (0.51 g) contained ca. 99% of
the cytotoxicity. It was dissolved in MeOH, coated on 10 g of
flash grade C18 media (YMC), and eluted with 200 mL each of
50% MeOH, 70% MeOH, 80% MeOH, 90% MeOH, and MeOH.
The 70% MeOH fraction was the most cytotoxic. HPLC of this
fraction in 25-mg aliquots on C18 (21 × 250 mm, 60 Å, Rainin
Dynamax column) using a linear 70-100% MeOH gradient
yielded 50 mg of schweinfurthin A (1), 38 mg of schweinfurthin
B (2), and 25 mg of schweinfurthin C (3).
Compound Data. Schweinfurthin A (1): NSC#696119;
yellowish solid; [R]D +51.8° (c 2.0, EtOH); UV (EtOH) λmax 224
nm (log ǫ 4.48), 331 nm (4.58); IR (film) 3419 (br), 1710, 1592,
1496, 1428, 1374, 1258, 1046, 959, 930 cm-1; 1H NMR 6.82 (d,
1H, J ) 16 Hz, H-1′), 6.80 (d, 1H, 2, H-6), 6.71 (d, 1H, 16,
H-2′), 6.69 (d, 1H, 2, H-8), 6.46 (s, 2H, H-4′, 8′), 5.25 (tq, 1H,
7.1, 1.2, H-2′′), 5.07 (t pentet, 1H, 7.1, 1.4, H-7′′), 4.13 (d, 1H,
2.4, H-3), 3.35 (m, 4H, H-2, 9a, 1′′), 2.71 (m, 2H, H-9), 2.35 (d,
1H, 13, H-4a), 2.04 (t, 2H, 7.3, H-6′′), 1.95 (t, 2H, 7.3, H-5′′),
1.94 (m, 1H, H-4), 1.76 (s, 3H, H-11), 1.62 (s, 3H, H-10′′), 1.56
(s, 3H, H-9′′), 1.40 (s, 3H, H-13), 1.08 (s, 3H, H-12), 1.07 (s,
3H, H-4′′); 13C NMR, see Table 1; HRFABMS (noba, positive
mode) M+ 548.3113 (calcd for C34H44O6 548.3138).
Schweinfurthin B (2): NSC#696118, yellowish solid; [R]D
+44.7° (c 1.0, EtOH), UV (EtOH) λmax 223 nm (log ǫ 4.44), 331
nm (4.52), IR (film) 3433 (br) 1708, 1588, 1493, 1431, 1374,
1257, 1156, 1086, 1043, 956, 909, 849 cm-1; 1H NMR (CD3OD,
500 MHz) δ 6.91 (1H d, J ) 2.0 Hz, H-6), 6.87 (1H d, J ) 16
Hz, H-1′), 6.83 (1H d, J ) 2.0 Hz, H-8), 6.77 (1H d, J ) 16 Hz,
H-2′), 6.47 (2H br s, H-4′ and H-8′), 5.25 (1H tq, J ) 7.2, 1.2
Hz, H-2′′), 5.07 (1H t pentet, J ) 7.2, 1.4 Hz, H-7′′), 4.14 (1H
q, J ) 3.4 Hz, H-3), 3.83 (3H s, 5-MeO-), 3.30 (obscured by
solvent, H-2 and H-1′′), 2.75 (2H m, H-9), 2.34 (1H dd, J )
13.9, 3.3 Hz, H-4), 2.05 (2H m, H-6′′), 1.94 (3H m, H-4a and
H-5′′), 1.76 (3H s, H-11), 1.74 (1H m, H-9a), 1.62 (3H s, H-10′′),
1.56 (3H s, H9′′), 1.40 (3H s, H-13), 1.10 (3H s, H-12), 1.08
(3H s, H-4′′); 13C NMR, see Table 1; FABMS (noba, positive
mode) 562, 532, 460, 407, 307, 289; HRFABMS (noba, positive
mode) M+ 562.3308 (calcd for C35H46O6 562.3294).
Schweinfurthin C (3): NSC#698298; UV λmax 330 nm (log
ǫ 4.03), EtOH, IR 3423 (br), 1590, 1499, 1440, 1302, 1036, 958,
849 cm-1; 1H NMR (CD3OD, 500 MHz) δ 6.81 (1H m, J ) 2.3
Hz, H-3), 6.77 (1H d, J ) 16 Hz, H-1′), 6.67 (1H m, J ) 6.3,
2.2 Hz, H-5), 6.63 (1H d, J ) 16 Hz, H-2′), 6.43 (2H s, H-4′
and H-8′), 5.33 (1H t, J ) 7.4, H-8), 5.24 (1H t, J ) 7.4 Hz,
H-2′′), 5.11 (1H t, J ) 7.2, H-13), 5.07 (1H t, J ) 7 Hz, H-7′′),
3.34 (obscured by solvent, H-7), 3.27 (obscured by solvent,
H-1′′), 2.11 (2H t, J ) 7.8 Hz, H-12a), 2.04 (4H t, J ) 7.8 Hz,
H-11 and H-6′′a), 1.93 (2H t, J ) 7.2 Hz, H-5′′), 1.75 (3H s,
H-4′′), 1.72 (3H s, H-10), 1.64 (3H s, H-16c), 1.62 (3H s, H-10′′c),
1.58 (3H s, H-15 b), 1.56 (3H s, H-9′′ b); 13C NMR (CD3OD, 125
MHz), δ 157.2 (2C s, C-5′ and C-7′), 146.1 (s, C-2), 144.2 (s,
C-1), 137.7 (s, C-3′), 136.6 (s, C-9), 134.8 (s, C-3′′), 132.2 (s,
C-14), 132.0 (s, C-8′′), 130.3 (s, C-4), 129.6 (s, C-6), 129.0 (d,
C-1′), 127.0 (d, C-2′), 125.5 (d, C-7′′), 125.3 (d, C-13), 124.6 (d,
C-2′′), 124.1 (d, C-8), 120.6 (d, C-5), 115.8 (s, C-6′), 111.0 (d,
C-3), 105.7 (2C d, C-4′ and C-8′), 41.0 (t, C-5′′), 40.9 (t, C-11),
29.1 (t, C-7), 27.8 (t, C-6′′a), 27.7 (t, C-12a), 25.9 (q, C-10′′c),
25.8 (q, C16c), 23.2 (t, C-1′′), 17.8 (q, C-9′′b), 17.7 (q, C-15b),
16.3 (q, C-4′′), 16.2 (q, C-10) (assignment of 1H and 13C signals with the same superscript may be reversed); FABMS
Journal of Natural Products, 1998, Vol. 61, No. 12 1511
(noba, positive mode) 516, 460, 393, 307, 289, 165; HRFABMS
516.3242 (calcd for C34H44O4 516.3240).
NCI 60-Cell Cancer Assay Data.17 The tumor cell line
subpanels are identified as follows: I (leukemia); II (lung,
nonsmall-cell); III (colon); IV (CNS); V (melanoma); VI (ovarian); VII (renal); VIII (prostate); IX (breast). The subpanel
and individual cell-line identifiers are given, along with the
corresponding negative log GI50, TGI, and LC50 values (molar),
respectively, for: schweinfurthin A (1) [I] CCRF-CEM (8.00,
5.68, 4.13), HL-60 (7.80, 6.89, 4.41), K-562 (7.19, 4.85, 4.14),
MOLT-4 (7.82, 5.89, 4.24), RPMI-8226 (8.00, 7.68, 4.12), SR
(7.15, 4.74, 4.13) [II] A549 (6.85,4.85, 4.39), EKVX (6.80, 4.82,
4.36), HOP-62 (6.92, 4.82, 4.32), HOP-92 (5.59, 4.82, 4.33),
NCI-H226 (5.35, 4.80, 4.15), NCI-H23 (5.49, 4.74, 4.29),
NCI-H322M (5.21, 4.68, 4.32), NCI-H460 (7.89, 4.92, 4.41),
NCI-H522 (5.59, 5.00, 4.57) [III] COLO205 (5.96, 5.55, 5.15),
HCC-2998 (6.30, 5.01, 4.48), HCT-116 (7.28, 4.85, 4.39), HCT15 (5.74, 5.22, 4.59), HT29 (6.51, 5.62, 5.26), KM12 (5.82, 4.85,
4.52), SW-620 (6.59, 4.74, 4.35) [IV] SF-268 (5.62, 4.68, 4.13),
SF-295 (7.96, 7.28, 4.77), SF-539 (8.00, 5.77, 5.09), SNB-19
(6.59, 4.70, 4.31), SNB-75 (7.82, 6.42, 4.30), U251 (7.60, 4.64,
4.31) [V] LOX IMVI (7.42, 4.77, 4.41), MALME-3M (5.37, 4.70,
4.27), M14 (7.80, 6.49, 5.57), SK-MEL-2 (5.77, 4.89, 4.37), SKMEL-28 (5.34, 4.62, 4.22), SK-MEL-5 (7.04, 5.55, 4.92), UACC257 (5.37, 4.74, 4.36), UACC-62 (6.96, 5.74, 5.20) [VI] IGROV1
(5.89, 4.96, 4.46), OVCAR-3 (5.51, 5.10, 4.66), OVCAR-4 (5.37,
4.62, 4.09), OVCAR-5 (5.19, 4.70, 4.34), OVCAR-8 (5.29, 4.70,
4.24), SK-OV-3 (5.57, 4.80, 4.40) [VII] 786-0 (8.00, 5.52, 4.72),
A498 (5.38, 4.64, 4.21), ACHN (5.68, 4.80, 4.40), CAKI-1 (6.89,
4.72, 4.25), RXF-393 (8.00, 5.68, 4.26), SN12C (5.16, 4.60, 4.21),
TK-10 (5.59, 4.77, 4.38), UO-31 (8.00, 6.68, 5.44) [VIII] PC-3
(6.77, 4.89, 4.44), DU-145 (5.92, 4.82, 4.27) [IX] MCF7 (7.57,
5.09, 4.07), MCF7/ADR-RES (5.42, 4.89, 4.38), MDA-MB-231
(5.38, 4.60, 4.15), HS 578T (8.00, 6.12, 4.06), MDA-MB-435
(5.42, 4.48, 4.13), MDA-N (5.55, 4.59, 4.21), BT-549 (4.89, 4.49,
4.13), T-47D (5.49, 4.66, 4.01).
Schweinfurthin B (2) [I] CCRF-CEM (6.64,5.20, 4.00), HL60 (7.43, 5.89, 4.00), K-562 (6.46, 5.21, 4.44), MOLT-4 (7.32,
5.28, 4.96), RPMI-8226 (7.82, 6.96, 4.92), SR (6.59, 4.92, 4.23)
[II] A549 (6.47,4.85, 4.41), EKVX (6.03, 4.85, 4.42), HOP-62
(6.07, 4.85, 4.39), HOP-92 (6.03, 4.89, 4.38), NCI-H226 (5.66,
4.85, 4.11), NCI-H23 (5.49, 4.72, 4.29), NCI-H322M (5.47,
4.77, 4.37), NCI-H460 (6.57, 4.89, 4.24), NCI-H522 (5.52,
4.77, 4.40) [III] COLO205 (6.21, 5.62, 5.17), HCC-2998 (5.44,
4.96, 4.46), HCT-116 (6.24, 5.18, 4.64), HCT-15 (5.72, 5.16,
4.47), HT29 (6.43, 5.68, 5.26), KM12 (5.89, 5.03, 4.74), SW620 (6.17, 5.51, 4.77) [IV] SF-268 (5.36, 4.62, 4.12), SF-295
(7.62, 6.54, 5.41), SF-539 (6.82, 5.70, 4.85), SNB-19 (6.40, 4.80,
4.39), SNB-75 (7.60, 5.74, 4.22), U251 (6.70, 4.62, 4.31) [V] LOX
IMVI (6.42, 4.77, 4.51), MALME-3M (5.06, 4.57, 4.16), M14
(6.85, 5.92, 5.38), SK-MEL-2 (5.74, 4.77, 4.33), SK-MEL-28
(5.96, 4.89, 4.28), SK-MEL-5 (6.68, 5.05, 4.54), UACC-257
(5.24, 4.68, 4.33), UACC-62 (6.48, 5.64, 5.00) [VI] IGROV1
(5.62, 4.74, 4.37), OVCAR-3 (5.41, 4.89, 4.37), OVCAR-4 (4.92,
4.30, 4.11), OVCAR-5 (5.15, 4.72, 4.35), OVCAR-8 (4.96, 4.57,
4.19), SK-OV-3 (5.59, 4.80, 4.39) [VII] 786-0 (7.66, 5.72, 4.85),
A498 (5.77, 4.77, 4.35), ACHN (5.37, 4.70, 4.36), CAKI-1 (5.72,
4.54, 4.12), RXF-393 (8.00, 6.57, 5.15), SN12C (4.92, 4.54, 4.17),
TK-10 (5.21, 4.66, 4.28), UO-31 (7.12, 6.04, 5.28) [VIII] PC-3
(6.60, 4.89, 4.37), DU-145 (5.47, 4.72, 4.30) [IX] MCF7 (6.70,
5.22, 4.41), MCF7/ADR-RES (5.16, 4.52, 4.12), MDA-MB-231
(5.19, 4.42, 4.09), HS 578T (7.70, 5.96, 4.00), MDA-MB-435
(5.12, 4.48, 4.14), MDA-N (5.47, 4.82, 4.54), BT-549 (4.96, 4.40,
4.08), T-47D (4.96, 4.16, 4.00).
Acknowledgment. We thank Jennifer Michael for technical help, Dominic Scudiero and Anne Monks for 60-cell cancer
tests, Tom McCloud for extraction of the plant material,
Duncan Thomas and Missouri Botanical Garden under contract to the National Cancer Institute for collection and
identification of the plant material, and Lewis Pannell for mass
spectra.
References and Notes
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1512 Journal of Natural Products, 1998, Vol. 61, No. 12
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Publication Date (Web): October 24, 1998 | doi: 10.1021/np980208m
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