Synthesis and cytotoxicity of novel 3-aryl-1-(3′-dibenzylaminomethyl- 4′-hydroxyphenyl)-propenones and related compounds

Abstract

The reaction of various 4′-hydroxychalcones (1a-e) with paraformaldehyde and dibenzylamine led to the formation of a novel series of 4′-hydroxy-3′-dibenzylaminomethyl chalcones (7a-e) instead of 4′-hydroxy-3′,5′-bis-(dibenzylaminomethyl)chalcones 4. In order to rationalise the formation of monoadduct 7, energy minimized model structures of 4a and 7a were compared. The in vitro cytotoxic activities of 7a-e were tested against PC-3 cell lines for the first time in this study and compared with the precursor 4′-hydroxychalcones (1a-e). Except for compound 7a (IC50: 19.85 μM), insertion of dibenzylaminomethyl function into 4′-hydroxychalcones resulted in complete loss of cytotoxic activity. The results suggested that it is not only the pKa but also the shape and size of the amine that is critical in governing the cytotoxic activity. © 2008 Pharmaceutical Society of Japan.