科研之友
微信
新浪微博
Facebook
分享链接
摘要
Actinomycins D-1-D-4 (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 D-1 (1) and D-2 (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 mu g/mL than those of 3-5 with MIC values of 0.5-1.0 mu g/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.
