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

A series of novel 1,9-disubstituted β-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 IC50 values of lower than 20 μM against ten human tumor cell lines. The results indicated that (1) the 3-chlorobenzyl and 3-phenylpropyl substituents in position-9 of β-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 CH2 units were more favorable. In addition, these compounds were found to exhibit remarkable DNA intercalating effects.

A series of 1,9-disubstituted β-carbolines was synthesized and evaluated as potential cytotoxic and DNA intercalating agents.Figure optionsDownload as PowerPoint slideHighlights
► 1,9-Disubstituted β-carbolines was synthesized and evaluated as antitumor agents.
► The 3-phenylpropyl substituents in position-9 were the suitable pharmacophoric group.
► The length of the alkylamino side chain moiety affected their cytotoxic potencies.
► These compounds were found to exhibit remarkable DNA intercalating effects.