Synthesis and biological evaluation of novel 3,9-substituted ß-carboline derivatives as anticancer agents.

In our previous studies on 1-benzyl-3-(5-hydroxymethyl-2-furyl)indazole (YC-1) analogs, we synthesised numerous substituted carbazole and α-carboline derivatives, which exhibited anticancer activity. In this study, we designed and synthesised a series of 3,9-substituted ß-carbolines, by replacing the tricyclic rings of carbazole and α-carboline derivatives with isosteric ß-carboline, and evaluated anticancer activity. We observed that 9-(2-methoxybenzyl)-ß-carboline-3-carboxylic acid (11a) inhibited the growth of HL-60 cells by inducing apoptosis, with a half maximal inhibitory concentration of 4.0 µM. Our findings indicate that ß-carboline derivatives can be used as lead compounds for developing novel antitumor agents.