Williams Philip G, Buchanan Greg O, Feling Robert H, Kauffman Christopher A, Jensen Paul R, Fenical William
Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California-San Diego, La Jolla, California 92093-0204, USA.
J Org Chem. 2005 Aug 5;70(16):6196-203. doi: 10.1021/jo050511+.
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.
对专性海洋放线菌热带盐孢菌（菌株CNB - 392）产生的次生代谢产物进行了广泛研究，该菌株是强效蛋白酶体抑制剂盐孢酰胺A（1）的产生菌，研究导致分离出了七种相关的γ-内酰胺。这些化合物中最重要的是盐孢酰胺B（3），它是1的去氯类似物，以及盐孢酰胺C（4），它是一种脱羧吡咯类似物。通过对人结肠癌细胞HCT - 116和美国国立癌症研究所的60细胞系面板进行广泛测试得出的所有八种化合物的新构效关系数据表明，氯乙基部分在1的增强活性中起主要作用。
