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Mar Drugs ; 18(11)2020 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-33167356

RESUMO

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.


Assuntos
Antineoplásicos/farmacologia , Toxinas Marinhas/farmacologia , Micromonosporaceae/metabolismo , Neoplasias/tratamento farmacológico , Antineoplásicos/isolamento & purificação , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Humanos , Toxinas Marinhas/isolamento & purificação , Estrutura Molecular , Neoplasias/patologia , Relação Estrutura-Atividade
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