3,5-Bis(arylidene)-4-piperidinones modified with bisphosphonate groups using a 1,2,3-triazole ring: Synthesis and antitumor properties

Abstract

An approach to the synthesis of new conjugates of 3,5-bis(arylidene)-4-piperidone pharmacophore with bisphosphonate moiety using a 1,2,3-triazole ring as a linker has been developed. The approach is based on a Cu(I)-catalyzed reaction of tetraethyl (but-3-yne-1,1-diyl)bisphosphonate with an alkyl azide containing a 3,5-bis(arylidene)-4-piperidone moiety. In vitro evaluation of antitumor activity of new conjugates 7a—d against human cancer cell lines HCT116 and MCF7 and human embryonic fibroblasts (HEF) has revealed that only compounds bearing strong electron-withdrawing substituents (cyano and nitro groups) in the aromatic rings possess moderate antitumor properties with the IC50 values ranging from 5 to 7.5 μmol L−1.