Kwon Hak Cheol, Kauffman Christopher A, Jensen Paul R, Fenical William
Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California at San Diego, La Jolla, California 92093-0204, USA.
J Am Chem Soc. 2006 Feb 8;128(5):1622-32. doi: 10.1021/ja0558948.
Four antitumor-antibiotics of a new structure class, the marinomycins A-D (1-4), were isolated from the saline culture of a new group of marine actinomycetes, for which we have proposed the name "Marinispora". The structures of the marinomycins, which are unusual macrodiolides composed of dimeric 2-hydroxy-6-alkenyl-benzoic acid lactones with conjugated tetraene-pentahydroxy polyketide chains, were assigned by combined spectral and chemical methods. In room light, marinomycin A slowly isomerizes to its geometrical isomers marinomycins B and C. Marinomycins A-D show significant antimicrobial activities against drug resistant bacterial pathogens and demonstrate impressive and selective cancer cell cytotoxicities against six of the eight melanoma cell lines in the National Cancer Institute's 60 cell line panel. The discovery of these new compounds from a new, chemically rich genus further documents that marine actinomycetes are a significant resource for drug discovery.
从一组新的海洋放线菌的盐培养物中分离出了四种具有新结构类型的抗肿瘤抗生素，即海制霉素A-D（1-4），我们已将该组海洋放线菌命名为“Marinispora”。海制霉素是由二聚体2-羟基-6-烯基-苯甲酸内酯与共轭四烯-五羟基聚酮链组成的不寻常的大环内酯类化合物，其结构通过光谱和化学方法相结合来确定。在室内光线下，海制霉素A会缓慢异构化为其几何异构体海制霉素B和C。海制霉素A-D对耐药性细菌病原体具有显著的抗菌活性，并且对美国国立癌症研究所60种细胞系面板中的八种黑色素瘤细胞系中的六种表现出令人印象深刻的选择性癌细胞细胞毒性。从一个新的、化学物质丰富的属中发现这些新化合物，进一步证明了海洋放线菌是药物发现的重要资源。
