Synthesis and biological evaluation of 1,9-disubstituted beta-carbolines as potent DNA intercalating and cytotoxic agents.

摘要

A series of novel 1,9-disubstituted beta-carbolines was designed, synthesized and evaluated as cytotoxic and DNA intercalating agents. Compounds 7b, 7c, 8b and 8c exhibited the most potent cytotoxic activities with IC(50) values of lower than 20 muM against ten human tumor cell lines. The results indicated that (1) the 3-chlorobenzyl and 3-phenylpropyl substituents in position-9 of beta-carboline nucleus were the suitable pharmacophoric group giving rise to significant antitumor agents; (2) the length of the alkylamino side chain moiety affected their cytotoxic potencies, and three CH(2) units were more favorable. In addition, these compounds were found to exhibit remarkable DNA intercalating effects.