New cytotoxic salinosporamides from the marine Actinomycete Salinispora tropica.
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.
Williams
Philip G
PG
Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California-San Diego, La Jolla, California 92093-0204, USA.
Buchanan
Greg O
GO
Feling
Robert H
RH
Kauffman
Christopher A
CA
Jensen
Paul R
PR
Fenical
William
W
D045744:Cell Line, Tumor; D006801:Humans; D007769:Lactams / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity*; D009682:Magnetic Resonance Spectroscopy; D008848:Micromonosporaceae / Q000737:chemistry* / Q000378:metabolism; D015394:Molecular Structure; D013329:Structure-Activity Relationship
D007769:Lactams; C504699:salinosporamide C; C504698:salinosporamide B