Synthesis and biological evaluation of a series of 2-(3,4,5-trimethoxybenzoyl)-indol-3-yl acetic acid derivatives as potential agents against human leukemia K562 cells

A series of 2-(3',4',5'-trimethoxybenzoyl)-indol-3-yl acetic acid derivs. 2a-g and 3a-j were synthesized and the effects of all the compds. on human leukemia K562 cell growth were investigated. The results showed that the presence of one or more electron-donating methoxy groups at 7- or 5- and 7- positions of N-Me indole ring, corresponding to compds. 3d and 3f, increased antiproliferative activity against K562 cells and induced the cell apoptosis. The results demonstrated that the methylation of the nitrogen atom of indole nucleus plays an important role for the anti-proliferative activities. Replacing the 3',4',5'-trimethoxybenzoyl functionality with a 3',4-dimethoxybenzoyl, 4'-methoxybenzoy or benzoyl group (compds. 3h-j, resp.) yielded inactive compds.