Synthesis and antiproliferative evaluation of 3-phenylquinolinylchalcone derivatives against non-small cell lung cancers and breast cancers

Certain 3-phenylquinolinylchalcone derivatives were synthesized and evaluated for their antiproliferative activities. Among them, (E)-3-(3-(4-methoxyphenyl)quinolin-2-yl)-1-phenylprop-2-en-1-one (6a) and (E)-1-(5-bromothiophen-2-yl)-3-(3-(4-methoxyphenyl)quinolin-2-yeprop-2-en-1-one (11) were identified as potential lead compounds for further development. Compound 6a was active against the growth of H1299 and SKBR-3 with IC50 values of 1.41 and 0.70 mu M respectively which was more active than the positive topotecan (IC50 values of 6.02 and 8.91 mu M respectively). Compound 11 exhibited an IC50 value of less than 0.10 mu M against the growth of MDA-MB231, and non-cytotoxic to the normal mammary epithelial cell (H184B5F5/M10). Mechanism studies indicated that compound 11 induced cell cycle arrest at G2/M phase followed by activation of caspase-3, cleavage of PARP, and consequently caused the cell death. (C) 2012 Elsevier Masson SAS. All rights reserved.