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

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• 作者：Aastha Singh ; Kaneez Fatima ; Ankita Srivastava ; Sadiya Khwaja ; Dev Priya ; Arjun Singh ; Girish Mahajan ; Sarfaraz Alam ; Ajit K. Saxena ; D. M. Mondhe ; Suaib Luqman ; Debabrata Chanda ; Feroz Khan and Arvind S. Negi
• 刊名：Chemical Biology & Drug Design
• 出版年：2016
• 出版时间：November 2016
• 年：2016
• 卷：88
• 期：5
• 页码：625-634
• 全文大小：964K
• ISSN：1747-0285

文摘

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.