New cytotoxic salinosporamides from the marine actinomycete Salinispora tropica

被引:145
作者
Williams, PG [1 ]
Buchanan, GO [1 ]
Feling, RH [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/jo050511+
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
An extensive study of the secondary metabolites produced by the obligate marine actinomycete Salinispora tropica (strain CNB-392), the producing microbe of the potent proteasome inhibitor salinosporamide A (1), has led to the isolation of seven related gamma-lactams. The most important of these compounds were salinosporamide B (3), which is the deschloro-analogue of 1, and salinosporamide C (4), which is a decarboxylated pyrrole analogue. New SAR data for all eight compounds, derived from extensive testing against the human colon carcinoma HCT-116 and the 60-cell-line panel at the NCI, indicate that the chloroethyl moiety plays a major role in the enhanced activity of 1.
引用
收藏
页码:6196 / 6203
页数:8
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