Anticancer activity of gallic acid template-based benzylidene indanone derivative as microtubule destabilizer

Benzylidene indanones have been designed and synthesized from gallic acid, a plant phenolic acid as possible anticancer agent. The best analogue of the series, that is, 3-(3',4',5'-trimethoxyphenyl)-4,5,6-trimethoxy-2-(4˝-nitrobenzylidene)-indan-1-one (8) exhibited potent cytotoxicity (IC₅₀ =3-10 μm) against several human cancer cell lines through microtubule destabilization (IC₅₀ =1.54 μm) after occupying colchicine-binding site of β-tubulin. In cell cycle analysis, compound 8 exerted G2/M phase arrest in both MCF-7 and MDA-MB-231 cells and induced apoptosis. It reduced 34.8% solid tumor in in vivo Ehrlich ascite carcinoma in Swiss albino mice at 30 mg/kg dose. In acute oral toxicity experiment, it was tolerable up to 300 mg/kg doses in Swiss albino mice. The lead compound 8 needs to be optimized for better activity.