Marinomycins A-D, antitumor-antibiotics of a new structure class from a marine actinomycete of the recently discovered genus "Marinispora"

被引:185
作者
Kwon, HC [1 ]
Kauffman, CA [1 ]
Jensen, PR [1 ]
Fenical, W [1 ]
机构
[1] Univ Calif San Diego, Scripps Inst Oceanog, Ctr Marine Biotechnol & Biomed, La Jolla, CA 92093 USA
关键词
D O I
10.1021/ja0558948
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
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.
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收藏
页码:1622 / 1632
页数:11
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