Anti-MRSA actinomycins D1-D4 from the marine sponge-associated Streptomyces sp. LHW52447 |
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Authors: | Wei-Hua Jiao Wei Yuan Zhi-Yong Li Jing Li Lei Li Jia-Bao Sun Yu-Han Gui Jie Wang Bo-Ping Ye Hou-Wen Lin |
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Institution: | 1. Research Center for Marine Drugs, State Key Laboratory of Oncogenes and Related Genes, Department of Pharmacy, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, People''s Republic of China;2. Institute of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, People''s Republic of China;3. Key Laboratory of Microbial Metabolism, Marine Biotechnology Laboratory, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, People''s Republic of China |
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Abstract: | Actinomycins D1?D4 (1–4), four new D-type actinomycin analogues, were isolated from the fermentation broth of a strain of marine sponge-associated Streptomyces sp. LHW52447, together with actinomycin D (5). The structures of 1?4 were determined by a combination analysis of HRMS and NMR spectroscopic methods, and their absolute configurations of amino acids were determined by Marfey's analysis. Actinomycins D1 (1) and D2 (2) are the first two naturally occurring actinomycins with incorporation an oxazole unit into the central phenoxazinone chromophore. Both 1 and 2 showed more potent antibacterial activities against three strains of pathogenic methicillin-resistant Staphylococcus aureus (MRSA) with MIC values of 0.125–0.25?μg/mL than those of 3?5 with MIC values of 0.5–1.0?μg/mL, which suggested that the anti-MRSA activity might be enhanced by the incorporation of an additional oxazole unit. In addition, the cytotoxicity evaluation against WI-38 human diploid lung fibroblasts revealed that the incorporation of oxazole unit could decrease the cytotoxicity of actinomycins on human normal cells. |
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Keywords: | Actinomycins Marine sponge Structural elucidation Anti-MRSA activity |
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