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-yl)prop-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 μM respectively which was more active than the positive topotecan (IC50 values of 6.02 and 8.91 μM respectively). Compound 11 exhibited an IC50 value of less than 0.10 μM 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.

Graphical abstractMechanism 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.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► A number of 3-phenylquinolinylchalcone derivatives have been synthesized. ► Compound 6a was more active than topotecan against the growth of H1299 and SKBR-3. ► Compound 11 was active against the growth of H1299, MCF-7, MDA-MB-231, and SKBR-3. ► Compound 11 induced cell cycle arrest at G2/M and consequently caused the cell death.