Anticancer activity of gallic acid template‐based benzylidene indanone derivative as microtubule destabilizer. (6th August 2016)

• Record Type: Journal Article
• Authors: Singh, Aastha; Fatima, Kaneez; Srivastava, Ankita; Khwaja, Sadiya; Priya, Dev; Singh, Arjun; Mahajan, Girish; Alam, Sarfaraz; Saxena, Ajit K.; Mondhe, D. M.; Luqman, Suaib; Chanda, Debabrata; Khan, Feroz; Negi, Arvind S.
• Is Part Of: Chemical biology & drug design. Volume 88:Number 5(2016)
• Page Start: 625
• Page End: 634
• Publication Date: 2016-08-06
• Subjects: benzylidene indanone -- cell cycle -- cytotoxicity -- Ehrlich ascite carcinoma -- tubulin polymerization inhibition; Drugs -- Design -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; 615.19005
• DOI: 10.1111/cbdd.12805
• Languages: English
• ISSNs: 1747-0277

Abstract

Abstract : 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, compound8 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 compound8 needs to be optimized for better activity. Abstract : 2‐Benzylidene indanones have been synthesized. The detailed pharmacology of the best analogue (Compound8 ) of the series has been explored.