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.
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Acknowledgements
The authors would like to thank the Department of Medicinal Chemistry, Ahvaz Jundishapur University of Medical Sciences and the Marine Pharmaceutical Science Research Center, Ahvaz Jundishapur University of Medical Sciences (Ahvaz, Iran) for support and help in performing this research.
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Manouchehrizadeh, E., Mostoufi, A., Tahanpesar, E. et al. Design, Synthesis, Molecular Docking and Biological Activity of New Piperidine and Piperazine Derivatives of Dichloroacetate as Potential Anticancer Agents. Pharm Chem J 54, 148–153 (2020). https://doi.org/10.1007/s11094-020-02172-4
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DOI: https://doi.org/10.1007/s11094-020-02172-4