Design, synthesis, cytotoxic activity, and molecular docking studies of indol and indazole-based stilbenes.

Abstract

To develop new highly effective anticancer agents derived from naturally occurring stilbene scaffold, in total of 25 indol and indazole-based stilbenes including 18 new compounds were designed according to molecular hybridization strategy and synthesized via Witting reaction. The synthesized derivatives were assayed for cytotoxic activities against human tumor cell lines (K562 cells and MDA-MB-231 cells) and normal cell line (L-02 cells). The biological screening results showed that indol and indazole-based stilbenes are of great interest for developing anticancer agents as eight derivatives possessed strong antiproliferative activities with IC50 values less than 10 µM. In particular, indol-based stilbene IS1l bearing piperidine exhibited the most potent cytotoxicity against both K562 and MDA-MB-231 cells with IC50 values 2.4 µM and 2.18 µM, respectively, along with a remarkable selectivity towards human normal L-02 cells. Moreover, molecular docking was exploited to elucidate the binding model of IS1l with biochemical target tryptophan 2,3-dioxygenase (TDO). Together, the results suggested that compound IS1l is a promising anticancer agent worthy of further investigation.