Verrucosamide,a Cytotoxic 1,4-Thiazepane-Containing Thiodepsipeptide from a Marine-Derived Actinomycete |
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| Authors: | Vimal Nair Min Cheol Kim James A Golen Arnold L Rheingold Gabriel A Castro Paul R Jensen William Fenical |
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| Institution: | 1.Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California, San Diego, CA 92093-0204, USA; (V.N.); (M.C.K.); (G.A.C.); (P.R.J.);2.Department of Chemistry and Biochemistry, University of California, San Diego, CA 92093, USA; (J.A.G.); (A.L.R.);3.Skaggs School of Pharmacy and Pharmaceutical Science, University of California, San Diego, CA 92093, USA;4.Moores Comprehensive Cancer Center, University of California, San Diego, CA 92093, USA |
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| Abstract: | A new cytotoxic thiodepsipeptide, verrucosamide (1), was isolated along with the known, related cyclic peptide thiocoraline, from the extract of a marine-derived actinomycete, a Verrucosispora sp., our strain CNX-026. The new peptide, which is composed of two rare seven-membered 1,4-thiazepane rings, was elucidated by a combination of spectral methods and the absolute configuration was determined by a single X-ray diffraction study. Verrucosamide (1) showed moderate cytotoxicity and selectivity in the NCI 60 cell line bioassay. The most susceptible cell lines were MDA-MB-468 breast carcinoma with an LD50 of 1.26 µM, and COLO 205 colon adenocarcinoma with an LD50 of 1.4 µM. Also isolated along with verrucosamide were three small 3-hydroxy(alkoxy)-quinaldic acid derivatives that appear to be products of the same biosynthetic pathway. |
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| Keywords: | marine actinomycetes cytotoxic thiodepsipeptides 1 4-thiazepane |
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