Synthesis of 4 '-hydroxy-3 '-piperidinomethylchalcone derivatives and their cytotoxicity against PC-3 cell lines

A new series of mono Mannich bases of 4'-hydroxychalcones 2a-e carrying a variety of aryl groups was synthesized and the in vitro cytotoxic activities of the new compounds were screened against PC-3 cell lines. Bioactivities of 2a-e, which are reported for the first time in this study, were compared against their precursor 4'-hydroxychalcones la-e. Compound 2b was found to be the most potent (IC50 = 3.7 mu M) among the compounds synthesized. In addition, the compounds la-c and 2d showed moderate cytotoxicity. Incorporation of the 3'-piperidinomethyl group in 1b and id raised the potency by 1.68 and 2.19 times respectively and, therefore, seemed to be a noteworthy molecular modification. Correlations were noted between cytotoxicity and one or more physiochemical constants of the aryl ring as well as log P values for the compounds 2a-e. The significant improvement of cytotoxicity of 2b, 2d, and 2e against PC-3 cell lines compared with their chalcone precursors suggests that the incorporation of a piperidinomethyl group is a useful molecular modification and further development of these compounds as candidate cytotoxic agents may be warranted.