Synthesis and cytotoxicity studies of thiazole analogs of the anticancer marine alkaloid dendrodoine

Abstract

The synthesis and cytotoxicity evaluation of 2-N,N-dimethylamino-5-indol-3-oylthiazole as the first member of a new portfolio of the thiazole analogs of the cytotoxic marine alkaloid dendrodoine (3-N,N-dimethylamino-5-indol-3-oyl-1,2,4-thiadiazole) is described. Exploiting the opportunity arising from the replacement of the thiadiazole ring of dendrodoine by a thiazole ring which allowed further substitution on the five-membered ring, 2-N,N-dimethylamino-5-indol-3-oyl-4-phenylthiazole has also been synthesized. Structural diversity is further extended by synthesizing 5-fur-2-oyl- and 5-coumarin-3-oyl-2-N,N-dimethylaminothiazoles, as well as 5-fur-2-oyl, 5-thiophen-2-oyl, 5-(1-methylbenzimidazol-2-oyl) and 5-benzothiazol-2-oyl derivatives of 2-N,N-dimethylamino-4-phenylthiazoles. Among these new N,N-dimethylaminothiazoles, 2-N,N-dimethylamino-5-indol-3-oyl-4-phenylthiazole shows significant in vitro cytotoxicity against a panel of human cancer cell lines.