Synthesis, biological evaluation and mechanism study of a class of benzylideneindanone derivatives as novel anticancer agents

Abstract

A series of new benzylideneindanone derivatives were designed, synthesized and evaluated as antitumor agents. Structure–activity relationship (SAR) studies showed that derivatives with 4,5,6-trimethoxyl on an indanone moiety displayed good anti-proliferative activities. Especially, compound 5a demonstrated the most potent inhibitory activity, with GI₅₀ values from 0.172 to 0.57 μM for five kinds of cancer cell lines. Further investigation showed that 5a could inhibit microtubule polymerization and thus induce G2/M phase arrest and apoptosis in A549 cells. Our findings revealed the benzylideneindanone moiety as a new attractive scaffold for mitosis-targeting drug discovery.