Synthesis and cytotoxic evaluation of 1-carboxamide and 1-amino side chain substituted beta-carbolines.

摘要

The condensation of alkylenediamine with ethyl beta-carboline-1-carboxylate and 1-bromo-beta-carboline gave beta-carboline-1-carboxamides and 1-amino-beta-carbolines, respectively. Some of these beta-carbolines were active against a panel of human tumor cell lines, and 1-amino derivatives were more potent than their 1-carboxamide congeners. In particular, among the 1-amino-beta-carbolines, the N(9)-arylated alkyl substituted beta-carbolines exhibited the most interesting cytotoxic activities with IC(50) value of lower than 20 muM. The preliminary structure-activity relationships (SARs) analysis suggested that (1) 1-amino substituents were the advisable pharmacophoric group for enhanced cytotoxic activities; (2) the introduction of appropriate arylated alkyl groups into position-9 of beta-carboline facilitated their cytotoxic potencies.