Antiproliferative properties of piperidinylchalcones.

Methoxylated chalcones bearing N-methylpiperidinyl substituents on ring A inhibited the growth of human tumour cell lines (MCF, HCT 116, and Jurkat) at IC50 values of <5 microM. Investigations on a representative member (12) showed that antiproliferative activity was linked to the disruption of the cell cycle at G1 and G2/M phases. The effect was concentration dependent and was evident at the approximate IC50 of 12. Down regulation of cell cycle regulatory components (CDK4, cyclin B, E2F, and phosphorylated Rb) were observed under similar conditions. Methoxylated chalcones without the piperidinyl substituent were found to exert equally potent and selective antiproliferative activity against HCT 116 tumour cells but did not interfere with cell cycle progression at their IC50 concentrations. The presence of the piperidinyl substituent in the chalcone template is proposed to lend specificity to the mechanism of antiproliferative activity, in addition to promoting a more desirable physicochemical profile.