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

被引：2

作者：

Manouchehrizadeh, Elham ^{[1
,2
]}

Mostoufi, Azar ^{[2
,3
]}

Tahanpesar, Elham ^{[2
]}

Fereidoonnezhad, Masood ^{[4
]}

机构：

[1] Islamic Azad Univ, Dept Chem, Khuzestan Sci & Res Branch, Ahvaz, Iran

[2] Islamic Azad Univ, Dept Chem, Ahvaz Branch, Ahvaz, Iran

[3] Ahvaz Jundishapur Univ Med Sci, Marine Pharmaceut Sci Res Ctr, Ahvaz, Iran

[4] Ahvaz Jundishapur Univ Med Sci, Sch Pharm, Dept Med Chem, Ahvaz, Iran

来源：

PHARMACEUTICAL CHEMISTRY JOURNAL | 2020年 / 54卷 / 02期

关键词：

dichloroacetate; cytotoxic activity; molecular docking; pyruvate dehydrogenase kinase inhibitors; IN-VITRO; BINDING; APOPTOSIS; CANCER; INHIBITORS; COMPLEXES; LIGANDS; ANALOGS;

D O I：

10.1007/s11094-020-02172-4

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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 mu M against HT-29 cell line.

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收藏

页码：148 / 153

页数：6

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