Design, synthesis and antiproliferative activity of functionalized flavone-triazole-tetrahydropyran conjugates against human cancer cell lines

Under optimized reaction conditions, an efficient synthetic method has been developed to afford the functionalized flavone-triazole-tetrahydropyran conjugates via click reactions. The Cu-catalyzed 1,3-dipolar cycloaddition reaction gave the pure products, 5-iodo- and 5-H-1-(tetrahydropyran)-1,2,3-triazol-4-(3-methoxylflavone) derivatives in excellent yield (90-98%) within 1-3 h. Further, Pd-catalyzed Suzuki coupling of 5-iodo-1,2,3-triazoles with phenylboronic acids afforded 5-phenyl-1-(tetrahydropyran)-1,2,3-triazol-4-(3-methoxylflavone) derivatives in excellent yield (93-95%) in 4-5 h. Products (3a-1, 4a-j) were screened in vitro for their anti-proliferative activity against three human cancer cell lines (MDA-MB 231, KCL22 and Hela). Compounds 3c, 3g, 3i, 3j, 4c and 4h have shown better cytotoxicity (IC50 0.61-1.68 mu M) than the reference drugs. Compounds 4e (IC50 0.70 mu M), 3j (IC50 0.61 mu M) and 4d (IC50 0.65 mu M) exhibited anti-proliferative activity better than the reference drugs against the MDA-MB 231 cells, KCL22 cells and HeLa cells respectively. (C) 2014 Elsevier Masson SAS. All rights reserved.