NPC Natural Product Communications EDITOR-IN-CHIEF DR. PAWAN K AGRAWAL Natural Product Inc. 7963, Anderson Park Lane, Westerville, Ohio 43081, USA agrawal@naturalproduct.us EDITORS PROFESSOR ALESSANDRA BRACA Dipartimento di Chimica Bioorganicae Biofarmacia, Universita di Pisa, via Bonanno 33, 56126 Pisa, Italy braca@farm.unipi.it PROFESSOR DEAN GUO State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100083, China gda5958@163.com PROFESSOR YOSHIHIRO MIMAKI School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Horinouchi 1432-1, Hachioji, Tokyo 192-0392, Japan mimakiy@ps.toyaku.ac.jp PROFESSOR STEPHEN G. PYNE Department of Chemistry University of Wollongong Wollongong, New South Wales, 2522, Australia spyne@uow.edu.au PROFESSOR MANFRED G. REINECKE Department of Chemistry, Texas Christian University, Forts Worth, TX 76129, USA m.reinecke@tcu.edu PROFESSOR WILLIAM N. SETZER Department of Chemistry The University of Alabama in Huntsville Huntsville, AL 35809, USA wsetzer@chemistry.uah.edu PROFESSOR YASUHIRO TEZUKA Institute of Natural Medicine Institute of Natural Medicine, University of Toyama, 2630-Sugitani, Toyama 930-0194, Japan tezuka@inm.u-toyama.ac.jp PROFESSOR DAVID E. THURSTON Department of Pharmaceutical and Biological Chemistry, The School of Pharmacy, University of London, 29-39 Brunswick Square, London WC1N 1AX, UK david.thurston@pharmacy.ac.uk HONORARY EDITOR PROFESSOR GERALD BLUNDEN The School of Pharmacy & Biomedical Sciences, University of Portsmouth, Portsmouth, PO1 2DT U.K. axuf64@dsl.pipex.com ADVISORY BOARD Prof. Berhanu M. Abegaz Gaborone, Botswana Prof. Viqar Uddin Ahmad Karachi, Pakistan Prof. Øyvind M. Andersen Bergen, Norway Prof. Giovanni Appendino Novara, Italy Prof. Yoshinori Asakawa Tokushima, Japan Prof. Lee Banting Portsmouth, U.K. Prof. Julie Banerji Kolkata, India Prof. Alejandro F. 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Tofazzal Islamb,c, Anja Schüfflerd and Hartmut Laatscha,* a Institute of Organic and Biomolecular Chemistry, University of Göttingen, Tammannstrasse 2, D-37077 Göttingen, Germany b Department of Crop Sciences, Plant Pathology and Plant Protection, Georg-August Universität Göttingen, Grisebachstraße 6, 3707 Göttingen, Germany c Current address: Department of Biotechnology, Bangabandhu Sheikh Mujibur Rahman Agricultural University, Gazipur-1706, Bangladesh d Institute of Biotechnology and Drug Research, D-67663 Kaiserslautern, Germany hlaatsc@gwdg.de Received: August 5th, 2010; Accepted: October 26th, 2010 Four isocoumarins have been isolated from the terrestrial Streptomyces sp. ANK302, namely 6,8-dimethoxy-3-methylisocoumarin (1), 6,8dihydroxy-3-methylisocoumarin (2), 6,8-dihydroxy-7-methoxy-3-methylisocoumarin (3), and 6,7,8-trimethoxy-3-methylisocoumarin (4). Compound 1 is a new naturally-occurring isocoumarin, and 2 was isolated as a new bacterial product. The structures 1-4 were deduced from high resolution mass, 1D and 2D NMR spectra and by comparison with related compounds from the literature. Compound 2 showed a strong zoosporicidal activity at a concentration of 5 µg/mL against a phytopathogenic oomycete, Plasmopara viticola, and 1 was active against Candida albicans. Keywords: terrestrial Streptomyces, isocoumarins, zoosporicide, oomycetes. Isocoumarins are not rare in plants and microorganisms and are forming an important class of compounds due to their broad biological activities, such as antimicrobial, antimalarial [1], antituberculous, cytotoxic, antifungal [2], immunomodulatory, and anti-inflammatory properties [3]. Isocoumarins are useful intermediates in the synthesis of a variety of natural products, including some isoquinoline alkaloids [4]. In plants, the number of coumarins is approximately three times higher than that of isocoumarins, but oppositely, in microorganisms, the latter group occurs three times more often [5-7]. During our investigation of the terrestrial Streptomyces sp. ANK302, four isocoumarins (1-4) were isolated. Compounds 2-4, including several related glycosides [8], had been described previously, but NMR data were not published. Interpretation of the HSQC and HMBC correlations (Figure 1), the molecular weights and corresponding formulas (by HRMS) unambiguously confirmed their structures and led to full assignment of their shift values. Compound 2 had been isolated previously from statically grown cultures of the fungus 5 R1O 3 7 1 R2 OR3 1: 2: 3: 4: CH3 O O R1 = CH3, R2 = H, R3 = CH3 R1 = R2 = R3 = H R1 = H, R2 = OCH3, R3 = H R1 = CH3, R2 = OCH3, R3 = CH3 Ceratocystis minor [9], the marine fungus Keissleriella sp. YS4108, and other fungi [10], while 3 and 4 have been isolated from an unidentified Streptomyces sp. [9]. 6,8Dimethoxy-3-methylisocoumarin (1) is a new natural product. 6,8-Dimethoxy-3-methylisocoumarin (1) was obtained as UV absorbing colorless solid of medium polarity, which exhibited a red color reaction with anisaldehyde/H2SO4 spraying reagent. A molecular weight of 220 Daltons was determined by EI MS, and the (+)-HRESI MS confirmed the molecular formula as C12H12O4. The 1H NMR spectrum of 1 displayed doublets (J = 2.3 Hz) of two m-coupled aromatic protons at δ 6.41 and 6.29; a further 1H singlet 46 Natural Product Communications Vol. 6 (1) 2011 Zinad et al. Experimental 5 O 3 H3C 1 7 CH3 5 HO 3 O 1 7 O H3C 1 CH3 O O OH O 2 Figure 1: Selected H,H COSY (↔) and HMBC (→) correlations of isocoumarins 1 and 2. appeared at δ 6.08. In the aliphatic region, two methoxysinglets at δ 3.95 and 3.88 and a resonance of an sp2-bound methyl singlet (δ 2.21) were visible. A combination of 13C and HSQC NMR spectra revealed all 12 carbon resonances of 1, four at chemical shifts indicative of oxygenated quaternary carbons in the aromatic region (δ 165.2, 163.1, 159.4, and 155.3), two quaternary carbons at δ 142.3, 102.7, and three methines at δ 103.6, 99.3 and 98.0. Of the remaining resonances, two could be attributed to methoxy groups at δ 56.2 and 55.6, and a methyl signal appeared at δ 19.5. Structure 1 was further confirmed by HMBC correlations (Figure 1): H-7 (δ 6.41) exhibited a 3J correlation with C-8a (δ 102.7) and CH-5 (δ 99.3) in the tetrasubstituted aromatic ring (Figure 1). The methine doublet of H-5 exhibited 3J couplings with the quaternary carbon atom C-8a and the methine carbon CH-7. H-5 (δ 6.29) displayed no COSY correlation with H-4, but showed a 3J coupling to CH-4 (δ 103.6) and vice versa, confirming a syn-periposition for both protons. The methyl group 3-CH3 showed a 4J COSY correlation with H-4, in addition to its 2J and 3 J HMBC correlations with C-3 and C-4, respectively. This resulted in structure 1. Crude extracts of Streptomyces sp. ANK302 and isolated compounds were tested for their effects on the motility behavior of the zoospores of the grapevine downy mildew pathogen, Plasmopara viticola [11]. The bioassay revealed that both the crude extract (100 μg/mL) and compound 2 (5 μg/mL) inhibited motility of P. viticola zoospores in a dose- and time-dependent manner. Zoospores became paralyzed (100 %) and then immobilized (100%) within 60 min in the presence of compound 2 at the dose of 5 µg/mL. Compound 4 (25 μg/mL) inhibited the motility of P. viticola zoospores in a dose- and time-dependent manner as well. Zoospores became paralyzed (ca. 98 %) and then immobilized (ca. 73%) within 60 min. This is the first report on the motility inhibitory and zoosporicidal effects of isocoumarins against the infecting propagules of an important oomycete phytopathogen, which is insensitive to most of the chemical fungicides [12]. Compound 1 also showed antifungal activity against Candida albicans by causing an inhibition zone of 12 mm at 40 μg/disk. The other compounds did not show activities in our tests. General: UV/vis spectra were recorded on a Varian Cary 3E UV/vis spectrometer. NMR spectra were measured on Bruker AMX 300 (300.135 MHz), Varian Unity 300 (300.145 MHz) and Varian Inova 500 (499.876 MHz) spectrometers. EIMS were recorded on a Finnigan MAT 95 (70 eV). HRMS were recorded by ESI MS on an Apex IV 7 Tesla Fourier-Transform Ion Cyclotron Resonance Mass Spectrometer (Bruker Daltonics, Billerica, MA, USA). Flash chromatography was carried out on silica gel (230-400 mesh). Thin layer chromatography (TLC) was performed on Polygram SIL G/UV254 (Macherey-Nagel & Co.). Rf values were measured on Polygram SIL G/UV254 (Macherey-Nagel & Co.) with CH2Cl2/5% MeOH. Size exclusion chromatography was carried out on Sephadex LH-20 (Lipophilic Sephadex, Amersham Biosciences Ltd.; purchased from Sigma-Aldrich Chemie, Steinheim, Germany). XAD-16 resin was obtained from Rohm and Haas, France. Isolation and taxonomy of Streptomyces sp. ANK302: The Streptomyces strain ANK302 has been derived from a soil sample and was isolated on YMG agar at room temperature (YMG agar: 2 g/L yeast extract, 5 g/L malt extract, 5 g/L glucose, 15 g/L agar, 30 mg/L cycloheximide). Its almost complete 16S rRNA gene sequence (GenBank Accession Nr. HM215581) shows high similarities to Streptomyces rectiverticillatus strain NRRL B-12369 (GenBank Accession Nr. DQ026657) and S. aureoversilis strain NBRC 13021 (GenBank Accession Nr. AB184855). The strain is deposited in the culture collection at the Institute of Organic and Biomolecular Chemistry, Göttingen, Germany. Fermentation: The terrestrial isolate Streptomyces sp. ANK302 was inoculated on M2 agar [13] from a soil storage culture and incubated for 96 h at 28°C. Three wellgrown Petri plates were used to inoculate 100 of 1 L Erlenmeyer flasks, each containing 250 mL of M2 medium, which were incubated as shake-cultures (95 rpm) at 28°C for 7 days. The resulting gray culture broth was mixed with ca. 1 kg diatomaceous earth (Celite) and pressed through a pressure filter affording the aqueous filtrate and the mycelial residue. The aqueous fraction was extracted with Amberlite XAD-16 resin and eluted using MeOH. The mycelium was extracted (3×) with EtOAc followed by acetone (1×). The acetone was evaporated and the aqueous residue extracted with EtOAc. Both organic phases were combined and evaporated to dryness, yielding 4.0 g of a brown extract, which was dissolved in methanol and extracted with cyclohexane to remove fats. Flash chromatography on silica gel with a MeOH/CH2Cl2 gradient (column 3 × 60 cm, 0 to 20 % MeOH) afforded 3 fractions. Fractions 1 and 2 were further purified on Sephadex LH-20 (MeOH) to deliver compounds 2 (12 mg) and 3 (6 mg), respectively, while fraction 3 was separated on Sephadex LH-20 (MeOH), followed by silica gel (cyclohexane/EtOAc gradient 0 to 100 % EtOAc), and Zoosporicidal isocoumarins again on Sephadex LH-20 (MeOH) to afford compounds 1 (5 mg) and 4 (10 mg). 6,8-Dimethoxy-3-methylisocoumarin (1) Colorless solid. Rf : 0.53 ( CH2Cl2/5% MeOH) UV λmax (MeOH) nm (log ε): 324 (3.80), 277 (3.91); λmax (MeOH/HCl) nm (log ε): 325 (3.72), 277 (3.84); λmax (MeOH/NaOH) nm (log ε): 322 (3.75), 278 (3.84). 1 H NMR (CDCl3, 300 MHz): δ 6.41 (1 H, d, J = 2.3 Hz, H-7), 6.29 (1 H, J = 2.3 Hz, H-5), 6.08 (1H, s, H-4), 3.95 (3H, s, 8-OCH3), 3.88 (3 H, s, 6-OCH3), 2.21 (3 H, s, 3-CH3). 13 C NMR (CDCl3, 125 MHz): δ 165.2 (Cq-6), 163.1 (Cq-8), 159.4 (CO-1), 155.3 (Cq-3), 142.3 (Cq-4a), 103.6 (CH-4), 102.7 (Cq-8a), 99.3 (CH-5), 98.0 (CH-7), 56.2 (8-OCH3), 55.6 (6-OCH3), 19.5 (3-CH3). EIMS (70 eV): m/z (%) 220 [M]+. (100), 191 (66), 149 (64), 43 (34); ESI HRMS m/z: [M+H]+ calcd for C12H13O4: 221.080835; found: 221.0809070; [M+Na]+ calcd for C12H12O4Na: 243.06278; found: 243.06287. 6,8-Dihydroxy-3-methylisocoumarin (2) Colorless solid. Rf : 0.29 (CH2Cl2/5% MeOH) 1 H NMR (DMSO-d6, 300 MHz): δ 10.95 (1H, brs, 8-OH), 6.43 (1 H, s, H-4), 6.31 (1 H, d, J = 2.1 Hz, H-5), 6.29 (1H, d, J = 2.1 Hz, H-7), 2.19 (3 H, s, 3-CH3). 13 C NMR (DMSO-d6, 125 MHz): δ 165.6 (CO-1), 165.2 (Cq-6), 162.5 (Cq-8), 153.8 (Cq-3), 139.4 (Cq-4a), 104.0 (CH-4), 102.3 (CH-5), 101.2 (CH-7), 97.0 (Cq-8a), 18.7 (CH3). EIMS (70 eV): m/z (%) 192 [M]+. (100), 177 (50), 150 (16), 121 (20); ESI HRMS m/z: [M+H]+ calcd for C10H9O4: 193.04953; found: 193.04950; [M+Na]+ calcd for C10H8O4Na: 215.03148; found: 215.03146. Natural Product Communications Vol. 6 (1) 2011 47 6,8-Dihydroxy-7-methoxy-3-methylisocoumarin (3) Colorless solid. Rf : 0.50 (CH2Cl2/5% MeOH). 1 H NMR (CD3OD, 300 MHz): δ 6.38 (1 H, s, H-5), 6.30 (1H, s, H-4), 3.84 (3 H, s, 7-OCH3), 2.19 (3 H, s, 3-CH3). 13 C NMR (CD3OD, 125 MHz): δ 168.2 (CO-1), 161.0 (Cq-6), 156.2 (Cq-8), 154.6 (Cq-3), 136.2 (Cq-4a), 135.5 (Cq-7), 105.3 (CH-4), 104.0 (CH-5), 100.0 (Cq-8a), 60.9 (7-OCH3), 19.1 (3-CH3). EIMS (70 eV): m/z (%) 222 [M]+. (100), 207 (90), 179 (60), 101 (38), 59 (44), 43 (34); ESI HRMS m/z: [M+H]+ calcd for C11H11O5: 223.060105; found: 223.0602940; [M+Na]+ calcd for C11H10O5Na: 245.042045; found: 245.0422940. 6,7,8-Trimethoxy-3-methylisocoumarin (4) Colorless solid. Rf : 0.55 (CH2Cl2/5% MeOH). 1 H NMR (CD3OD, 300 MHz): δ 6.75 (1 H, s, H-5), 6.29 (1 H, s, H-4), 3.93 (3 H, s, 6-OCH3), 3.88 (3 H, s, 8-OCH3), 3.82 (3 H, s, 7-OCH3), 2.20 (3 H, s, 3-CH3). 13 C NMR (CD3OD, 125 MHz): δ 161.6 (CO-1), 160.9 (Cq-6), 156.3 (Cq-8), 155.4 (Cq-3), 143.4 (Cq-7), 138.2 (Cq-4a), 107.7 (Cq-8a), 104.6 (CH-4), 104.0 (CH-5), 62.3 (8-OCH3), 61.6 (7-OCH3), 56.8 (6-OCH3), 19.3 (CH3-9). EIMS (70 eV): m/z (%) 250 [M]+. (56), 235 (100), 207 (40), 43 (36); ESI HRMS m/z: [M+H]+ calcd for C13H15O5: 251.09140; found: 251.09154; [M+Na]+ calcd for C13H14O5Na: 273.07334; found: 273.07350. Acknowledgment - We thank Dr H. Frauendorf and R. Machinek for the mass and NMR spectra, F. Lissy and A. 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The pH of the solution was adjusted to 7.8 and sterilized by autoclaving for 30 minutes at 121°C and 1.2 bar. Natural Product Communications Vol. 6 (1) 2011 Published online (www.naturalproduct.us) Chemical Variability of Essential Oils in Natural Populations of Cupressus dupreziana Messaoud Ramdani, Takia Lograda, Pierre Chalard, Jean Claude Chalchat and Gilles Figueredo 87 Composition of a Monoterpenoid-rich Essential Oil from the Rhizome of Zingiber officinale from North Western Himalayas Suphla Gupta, Pankaj Pandotra, Gandhi Ram, Rajneesh Anand, Ajai Prakash Gupta, Mohd. Kashif Husain, Yashbir Singh Bedi and Gopal Rao Mallavarapu 93 Chemical Composition of the Essential Oil of Croton gossypiifolius from Venezuela Alírica I. Suárez, Marly Oropeza, Luís Vásquez, Stephen Tillett and Reinaldo S. Compagnone 97 Volatile Constituents of Festuca nigrescens, Phleum alpinum and Poa alpina from N.W. Italian Alpine Pastures Aldo Tava, Roberto Cecotti, Maris Grecchi, Luca Falchero, Mauro Coppa and Giampiero Lombardi 101 Comparison of Eucalyptus cinerea Essential Oils Produced by Hydrodistillation and Supercritical Carbon Dioxide Extraction Tavleen S. Mann, Garikapati D. Kiran Babu, Shailja Guleria and Bikram Singh 107 2-Undecanone Rich Leaf Essential Oil from Zanthoxylum armatum Deepa Bisht and Chandan S. Chanotiya 111 Chemical Composition of the Essential Oil of Cachrys libanotis from Algeria Nabila Bouderdara, Abdelhakim Elomri, Lakhdar Djarri, Kamel Medjroubi, Elisabeth Seguin and Philippe Vérité 115 The Essential Oil of Artemisia scoparia from Tajikistan is Dominated by Phenyldiacetylenes Farukh S. Sharopov and William N. Setzer 119 Chemical Composition of Essential Oil of Senecio coincyi, an Endemic Species of the Central Iberian Peninsula Carlos Arrabal, Felipe Martínez García, María Paz Arraiza and Silvia Guerrero García 123 Chemical Composition of the Essential Oil from Carramboa littlei (Asteraceae) Yndra Cordero de Rojas, Luis B. Rojas and Alfredo Usubillaga 127 Terpenoid Compositions and Antioxidant Activities of Two Indian Valerian Oils from the Khasi Hills of North-east India Jayashankar Das, Ashiho A. Mao and Pratap J. Handique 129 Composition, Antioxidant and Antimicrobial Activities of the Seed Essential Oil of Calocedrus formosana from Taiwan Chen-Lung Ho, Yen-Hsueh Tseng, Eugene I-Chen Wang, Pei-Chun Liao, Ju-Ching Chou, Chien-Nan Lin and Yu-Chang Su 133 Comparison of Volatile Constituents, and Antioxidant and Antibacterial Activities of the Essential Oils of Thymus caucasicus, T. kotschyanus and T. vulgaris Shiva Asbaghian, Ali Shafaghat, Khalil Zarea, Fakhraddin Kasimov and Farshid Salimi 137 Chemical Composition and Antimicrobial Activity of the Essential Oil of the Leaves of Feronia elephantum (Rutaceae) from North West Karnataka Rajesh K. Joshi, Vijayalaxmi M. Badakar, Sanjiva D. Kholkute and Nayeem Khatib 141 Leaf Essential Oil of Manekia naranjoana (Piperaceae) from Costa Rica and its Cytotoxic Activity Carlos Chaverri, Cecilia Díaz and José F. Cicció 145 Review/Account Anthocyanins as Antimicrobial Agents of Natural Plant Origin Agnieszka Cisowska, Dorota Wojnicz and Andrzej B. Hendrich 149 Natural Product Communications 2011 Volume 6, Number 1 Contents Original Paper Page A New Eudesmane Sesquiterpene from Pluchea arguta Nikhat Saba, Rasheeda Khatoon, Viqar Uddin Ahmad and Saleha Suleman Khan 1 Bioactive Diterpenes from Clerodendrum kaichianum Mingfeng Xu, Lianqing Shen, Kuiwu Wang, Qizhen Du and Nan Wang 3 Multi-stage Mass Spectrometric Analysis of Saponins in Glycyrrhiza radix Ken Tanaka, Kosuke Hayashi, Abrar Fahad and Masanori Arita 7 5–Methoxyaristololactam I, the First Natural 5–Substituted Aristololactam from Asarum ichangense Bai–Bo Xie, Ming–Ying Shang, Kuo–Hsiung Lee, Xuan Wang, Katsuko Komatsu and Shao–Qing Cai 11 Flavonoid Aglycones from the Leaf and Stem Exudates of Some Geraniaceae Species Eckhard Wollenweber, Marion Dörr and Matthias Christ 15 Qualitative and Quantitative Analysis of the Major Bioactive Phenolic Compounds of Glechoma longituba by LC-Coupled with PAD and ESI-MS Detection Shu-mao Ni, Da-wei Qian, Jin-ao Duan, Nian-yun Yang and Jian-ming Guo 17 n Phenolic Compounds of Mountain Tea from the Balkans: LC/DAD/ESI/MS Profile and Content Jasmina Petreska, Gjose Stefkov, Svetlana Kulevanova, Kalina Alipieva, Vassya Bankova and Marina Stefova 21 Facile Synthesis of Chrysin-derivatives with Promising Activities as Aromatase Inhibitors Hamdoon A. Mohammed, Lalla A. Ba, Torsten Burkholz, Elena Schumann, Britta Diesel, Josef Zapp, Alexandra K. Kiemer, Christina Ries, Rolf W. Hartmann, Mohammed Hosny and Claus Jacob 31 Anthocyanins from Fuchsia Flowers Monica Jordheim, Irene Skaar, Helene Lunder and Øyvind M. Andersen 35 Oxyresveratrol Protects Against DNA Damage Induced by Photosensitized Riboflavin Manussanunt Chatsumpun, Taksina Chuanasa, Boonchoo Sritularak and Kittisak Likhitwitayawuid 41 Bioactive Isocoumarins from a Terrestrial Streptomyces sp. ANK302 Dhafer Saber Zinad, Khaled A. Shaaban, Muna Ali Abdalla, Md. Tofazzal Islam, Anja Schüffler and Hartmut Laatsch 45 Aromatic Compounds from the Liverwort Conocephalum japonicum Na Liu, Dong-Xiao Guo, Yan-Yan Wang, Li-Ning Wang, Mei Ji and Hong-Xiang Lou 49 New Stress Metabolite from Bulbophyllum kwangtungense Jianbo Chen, Huifang Zhang, Li Chen and Bin Wu 53 In vitro Antioxidant Activities of Maillard Reaction Products Produced in the Steaming Process of Polygonum multiflorum Root Zhenli Liu, Yuanyan Liu, Zhimao Chao, Zhiqian Song, Chun Wang and Aiping Lu 55 Targets of Red Grapes: Oxidative Damage of DNA and Leukaemia Cells Jaouad Anter, Noriluz de Abreu-Abreu, Zahira Fernández-Bedmar, Myriam Villatoro-Pulido, Ángeles Alonso-Moraga and Andrés Muñoz-Serrano 59 Extraction and Identification of Isothiocyanates from Broccolini Seeds Bochao Zhang, Xiaoqin Wang, Yanjing Yang and Xuewu Zhang 65 Authentication of Chinese Crude Drug Gecko by DNA Barcoding Hai-Feng Gu,Yun Xia, Rui Peng, Bang-Hui Mo, Li Li and Xiao-Mao Zeng 67 Comparative Biochemical Characterization of 5'-Phosphodiesterase and Phosphomonoesterase from Barley Malt Sprouts Suncica Beluhan and Vladimir Maric 73 Traditional Medicine in Syria: Folk Medicine in Aleppo Governorate Amal Alachkar, Ahmad Jaddouh, Muhammad Salem Elsheikh, Anna Rita Bilia and Franco Francesco Vincieri 79 Essential Oil Composition of Vismia macrophylla Leaves (Guttiferae) Janne Rojas, Alexis Buitrago, Luis Rojas and Antonio Morales 85 Continued Overleaf