Modification of 3,5-bis(arylidene)-4-piperidone pharmacophore by phosphonate group using 1,2,3-triazole cycle as a linker for the synthesis of new cytostatics

Abstract

Novel cytotoxic 3,5-bis(arylidene)-4-piperidones conjugated with phosphonate groups via 1,2,3-triazole ring have been synthesized and their antitumor properties have been evaluated. Synthetic route to these conjugates is based on 1,3-cycloaddition of diethyl (ω-azidoalkyl)phosphonates to 1-prop-2-ynyl-piperidin-4-one in the presence of Cu(I) catalyst followed by crotonic condensation of resulting 1,2,3-triazole with aromatic aldehydes. The synthesized phosphonate derivatives of 3,5-bis(arylidene)-4-piperidone series displayed high in vitro inhibitory properties toward HCT116 and MCF7 as well as CaoV3, A549, and PC3 human cancer cell lines with IC50 values in the range of 1.5–8.0 μM.