Design, Synthesis, Molecular Docking and Biological Activity of New Piperidine and Piperazine Derivatives of Dichloroacetate as Potential Anticancer Agents

Dichloroacetate (DCA) is a small anticancer agent acting through inhibition of pyruvate dehydrogenase kinases (PDKs) and preventing proliferation of tumor growth. In this study, a series of new piperidine and piperazine derivatives of DCA were designed and subjected to molecular docking analysis. Based on the docking results, nine compounds with a lowest binding energy and better interaction with PDK isoenzymes were selected and synthesized. The cytotoxic activities of the synthesized compounds were evaluated against HT-29 and MCF7 human cancer cell lines. These compounds showed moderate potency and much higher anticancer activity than DCA. The most active compound of the series (f1) showed IC50 value of 7.79 μM against HT-29 cell line.