Bangladesh Journal of Pharmacology Volume: 15; Number 2; Year 2020 Cite this article as: Huyena VTT, Minh LTH, Quyen VT, Anh NM, Cuc NTK, Luyen NT, Dat NT. Antimicro- bial metabolites from Streptomyces sp. strain PDH23 derived from marine sponge Rhabdastrella globostella- ta. Bangladesh J Pharmacol. 2020; 15: 69-70. Antimicrobial metabolites from Streptomy- ces sp. strain PDH23 derived from marine sponge Rhabdastrella globostellata Sir, Sponge-associated bacterial community has shown great potential as a source of biologically active constituents. The marine sponge Rhabdastrella globos- tellata has been known to display potent anti-cancer effects (Hirashima et al. 2010; Li et al., 2010, Aoki et al., 2007). Pandey et al. (2014) revealed that 18 of 127 microorganisms isolated from R. globostellata exhibited acetylcholinesterase inhibitory activity. However, the antimicrobial activity of R. globostellata associated bacteria has not been reported so far. In our search for antibacterial agents from marine organisms, the strain of Streptomyces sp. PDH23 isolated from R. globostellata, which was collected at depth of 10 m in Da Nang sea, Vietnam, was found to exhibit remarkable antimicrobial activity against Bacillus cereus (ATCC14579) and Candida albicans (ATCC1023) (see supplemental data). The cultured broth of PDH23 strain (50 L) was extracted with ethyl acetate (30 L x 3 times), the organic layers were combined and concentrated to obtain crude extract. A half of the extract was fractionated in a silica gel column eluted with a gradient of 0-100% methanol in dichloromethane to afford eight fractions F1-8. The fraction F1 was chromatographed on a silica gel column eluted with n -hexane:acetone (3:1, v/v) to give four subfrations F1.1-1.4. Compound 2 (p-hydroxybenzaldehyde, 5.8 mg) and 3 (indole -3-carboxaldehyde, 6.2 mg) were respectively isolated from the subfractions F1.2 and F1.4 by a silica gel column using dichloromethane:ethyl acetate (20:1, v/v). Cyclo(D-Pro-D- Val)(4) (22 mg) was purified from F2 through a Sephadex LH-20 column eluted with methanol:water (1:1, v/v). Fraction F5 was passed through a silica gel column to afford four subfractions F5.1-5.4. Compound 1 (11.6 mg) was isolated from F5.3 by silica gel column chromatography using dichloromethane:methanol (3:1, v/v) and 5 (uracil, 6.5 mg) was purified from F5.4 by a Sephadex LH-20 eluted with methanol:water (1:1, v/v) (Figure 1). Compound 1 was obtained as a colorless solid. Its HR- ESI-MS revealed an ion peaks at m/z 307.1385 [M + H]+, which confirmed the molecular formula of C13H22O8 of 1. The 1H-NMR spectrum of 1 showed the presence of two methyl groups at δH 1.40 (3H, br d, J = 6.5 Hz, H-6) and 1.46 (3H, br s, H-7), an anomeric signal at δH 4.48 (1H, d, J = 8.0, H-1) characteristic for a β-glycosyl unit. The 13C NMR and DEPT spectra of 1 showed the presence of 13 signals including a carboxylic, an oxygenated quaternary carbon, six oxygenated methine and three methylene groups. Six signals at δC 98.5 (C-1'), 74.9 (C-2'), 77.8 (C-3'), 72.0 (C-4'), 78.0 (C-5'), and 63.3 (C -6') were assigned to a glucose moiety. Acid hydrolysis follwed by HPLC analysis allowed to determined the glucosidic unit as β-D-glucopyranoside (Thai et al., 2017). According to the mass spectral data which indicated three double bond equivalents (DBE) in the structure of 1, the remaining 13C signals should be cyclized since 2 DBEs were attributed to a carboxylic group and a glucopyranoside ring. The HMBC correlations showed the coupling from H-2 (δH 2.78 and 2.86) to C-1 (δC 175.1) and C-3 (δC 76.6); from H-7 (δH 1.46) to C-2 (δC 42.6) C-3 and C-4 (δC 45.1); from H-6 (δH 1.40) to C-4 and C-5 (δC 74.9). The correlation from the anomeric proton H-1' (δH 4.48) to C-3 suggested that the glucosidic moiety attached to C-3. Thus compound 1 was elucidated to be 3-methyl-5-hexanolide 3-O--D- glucopyranoside. The relative configuration of 1 was determined based on the proton coupling constants and NOESY experiments. The coupling constant between H -5 and H-4a and H-4b were 11.5 and 3.5 Hz, corresponding to di-axial and axial-equatorial relationship, respectively (Breitmaier, 2002). Thus the proton H-5 was in axial orientation. The obvious coupling between H-5 and H-7 suggested that H-7 was in axial position. The antimicrobial activity of the isolated compounds was evaluated. A Journal of the Bangladesh Pharmacological Society (BDPS) Bangladesh J Pharmacol 2020; 15: 69-70 Journal homepage: www.banglajol.info Abstracted/indexed in Academic Search Complete, Agroforestry Abstracts, Asia Journals Online, Bangladesh Journals Online, Biological Abstracts, BIOSIS Previews, CAB Abstracts, Current Abstracts, Directory of Open Access Journals, EMBASE/Excerpta Medica, Global Health, Google Scholar, HINARI (WHO), International Pharmaceutical Abstracts, Open J-gate, Science Citation Index Expanded, SCOPUS and Social Sciences Citation Index ISSN: 1991-0088; DOI: 10.3329/bjp.v15i2.44526 Letter to the Editor This work is licensed under a Creative Commons Attribution 4.0 International License. You are free to copy, distribute and perform the work. You must attribute the work in the manner specified by the author or licensor CH3 O HO HO HO OH O O O O O O H CH3 H H H H 2 3 4 5 6 7 1 2 3 1 4 1΄ 2΄ 3΄ 4΄ 5΄ 6΄ 5 6 7 Glu O HO O N H O O HN N O NH N H O 2 3 4 5 Figure 1: Structure of the compounds 1-5 and key HMBC (→) and NOESY (<--->) correlations of 1 The antimicrobial activity of the isolated compounds was evaluated against Candida albicans and Bacillus cereus (Teh et al., 2013). Compound 1 showed moderate effect with MIC values of 256 μg/mL and 512 μg/mL, respectively (Table I). Interestingly, the growths of the microorganism were completely inhibited when treated with the combination of 1 (128 μg/mL) and 2 (32 μg/ mL for C. albicans and 64 μg/mL for B. cereus). This work was supported by Graduate University of Science and Technology, Vietnam Academy of Science and Technology (grant code: GUST.STS.ĐT2017-SH01). Conflict of Interest: Nil Vu Thi Thu Huyen1,2, Le Thi Hong Minh2, Vu Thi Quyen2, Nguyen Mai Anh2, Nguyen Thi Kim Cuc2, Nguyen Thi Luyen3, Nguyen Tien Dat3 1Graduate University of Science and Technology, VAST, 18 Hoang Quoc Viet, CauGiay, Hanoi, Vietnam; 2Institute of Marine Biochemistry, Vietnam Academy of Science and Technology (VAST), 18 Hoang Quoc Viet, CauGiay, Hanoi, Vietnam; 3Center for Research and Technology Transfer, VAST, 18 Hoang Quoc Viet, CauGiay, Hanoi, Vietnam. Corresponding author: email: ngtiend@imbc.vast.vn References Aoki S, Sanagawa M, Watanabe Y, Setiawan A, Arai M, Koba- yashi M. Novel isomarabarican triterpenes, exhibiting selective antiproliferative activity against vascular endo- thelial cells, from marine sponge Rhabdastrella globostellata. Bioorg Med Chem. 2007; 15: 4818-28. Breitmaier E. Structure elucidation by NMR. In: Organic chemistry: A practical guide. 3rd ed. John Wiley & Sons, Chichester, 2002. 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Thai TH, Hai NT, Hien NT, Ha CTT, Cuong NT, Binh PT, Dang NH, Dat NT. Cytotoxic constituents of Mallotus microcarpus. Nat Prod Commun. 2017; 12: 407-08. 70 Bangladesh J Pharmacol 2020; 15: 69-70 Table I Antimicrobial activity of the isolated compounds Compounds MIC (μg/mL) Candida albicans Bacillus cereus Compound 1 256 512 Compound 2 1024 512 Both 128 (1) + 32 (2) 128 (1) + 64 (2) Nystatin 8.0 - Chloramphenicol - 2.5 Supplementary File mailto:ngtiend@imbc.vast.vn