1,5-Diaryl-3-oxo-1,4-pentadienes based on (4-oxopiperidin-1-yl)(aryl)methyl phosphonate scaffold: synthesis and antitumor properties

Novel 3,5-bis(arylidene)-4-piperidones modified with diethyl[(aryl)methyl]phosphonate moiety attached to the piperidone nitrogen atom have been synthesized by crotonic condensation of aromatic aldehydes with diethyl[(4-oxopiperidin-1-yl)(aryl)methyl]phosphonates in the presence of LiClO4/Et3N system or acetonitrile solution of boron trifluoride etherate. The synthesized phosphonate derivatives of 3,5-bis(arylidene)-4-piperidone series displayed inhibitory properties toward RD, PC3, HCT116, and MCF7 human cancer cell lines with IC50 values in the range of 2.5–8.5 μM, as assessed by an in vitro 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay.