Synthesis and anticancer activity of 2-benzylidene indanones through inhibiting tubulin polymerization

• Published in: Bioorganic & medicinal chemistry 2012-05, Vol.20 (9), p.3049-3057
• Main Authors: Prakasham, A.P., Saxena, A.K., Luqman, Suaib, Chanda, Debabrata, Kaur, Tandeep, Gupta, Atul, Yadav, D.K., Chanotiya, C.S., Shanker, Karuna, Khan, F., Negi, Arvind S.
• Format: Article
• Language: English
• Subjects: Acute oral toxicity; Administration, Oral; Animals; Anticancer; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Antitumor activity; Antitumor agents; Benzodioxoles; Benzylidene Compounds - chemical synthesis; Benzylidene Compounds - chemistry; Benzylidene Compounds - pharmacology; Binding Sites; Biological and medical sciences; Cancer; Cell Line, Tumor; Cell Proliferation - drug effects; Computer Simulation; Cytotoxicity; Gallic acid; Humans; Indanones; Indans - chemical synthesis; Indans - chemistry; Indans - pharmacology; Medical sciences; Mice; Pharmacology. Drug treatments; Polymerization; Protein Structure, Tertiary; Toxicity; Tubulin; Tubulin - chemistry; Tubulin - metabolism; Tubulin Modulators - chemical synthesis; Tubulin Modulators - chemistry; Tubulin Modulators - pharmacology; Tubulin polymerization inhibition; Tumor cell lines
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2012.02.057

Gallic acid has been modified to 2-benzylidene indanones. Three of the analogues exhibited potent anticancer activity (IC50 in nM) through tubulin polymerization inhibition. In an attempt to discover a potent and selective anticancer agent, gallic acid has been modified to benzylidene indanones as tubulin polymerization inhibitors. These compounds were evaluated against several human cancer cell lines and also evaluated for inhibition of tubulin polymerase in in vitro assays. Three of the analogues exhibited strong cytotoxicity against human cancer cell lines IC50=10–880nM and also showed tubulin polymerization inhibition (IC50=0.62–2.04μM). Compound 9j, the best candidate of the series was found to be non-toxic in acute oral toxicity in Swiss-albino mice up to 1000mg/kg dose.