New palbociclib analogues modified at the terminal piperazine ring and their anticancer activities

•New palbociclib analogues by extensive functionalization of the tail piperazine ring were synthesized.•All compounds were evaluated in MCF-7 cell line.•Compound 4e exhibited robust tumor growth inhibition in vitro and vivo.

A series of new palbociclib analogs by extensive functionalization of the tail piperazine ring with various carbamates and amides have been synthesized. All the palbociclib derivatives were evaluated for their cytotoxic activities against MCF-7 cell line. From the anti-proliferation activity results, two of the tested compounds (compounds 4d and 4e) showed significant cytotoxic effects. And compounds 4d and 4e exhibited potent anticancer activities in MDA-MB-453 and MDA-MB-231 cells. Among these derivatives compound 4e was found to possess cytotoxicity that is better than standard drug palbociclib. Moreover, compound 4e demonstrated robust tumor growth inhibition in vivo model.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slide