Novel potent antimitotic heterocyclic ketones: synthesis, antiproliferative activity, and structure-activity relationships

Abstract

We report the synthesis, antiproliferative activity, and SAR of novel heterocyclic ketones derived from carbazole sulfonamides. Most of the heterocyclic ketones showed strong cytotoxicities. (N-1-Methylindole-5-yl)-(3,4,5-trimethoxyphenyl)-methanone 8b gave the most potent cytotoxicity (9.2-26 nM) against seven human tumor cell lines. The mechanism of action of the heterocyclic ketones appears to involve targeting of tubulin, similar to that of CA-4 and different from the carbazole sulfonamides.