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Synthesis of N-Substituted Benzamide Derivatives and their Evaluation as Antitumor Agents

[ Vol. 16 , Issue. 4 ]

Author(s):

Taiping Chen, Hongwu Jiang, Jianjun Zhou, Zicheng Li*, Wencai Huang, Youfu Luo and Yinglan Zhao   Pages 555 - 562 ( 8 )

Abstract:


Background: Histone deacetylases inhibitors (HDACIs) with different chemical structures have been reported to play an important role in the treatment of cancer.

Objective: The study aims to modify the structure of Entinostat (MS-275) to discover new compounds with improved anti-proliferative activities and perform SAR studies on this class of bioactive compounds.

Methods: Fourteen N-substituted benzamide derivatives were synthesized and their antiproliferative activities were tested with four cancer cell lines (MCF-7, A549, K562 and MDA-MB- 231) by MTT assay.

Results: Compared with MS-275, six compounds exhibited comparable or even better antiproliferative activities against specific/certain cancer cell lines.

Conclusion: The preliminary SARs showed that (ⅰ) the 2-substituent of the phenyl ring in the R group and heteroatoms of amide which can chelate with zinc ion are critical to the antiproliferative activity and (ⅱ) chlorine atom or nitro-group on the same benzene ring largely decreases their anti-proliferative activity. Molecular docking study illustrated the interaction (binding affinity) between the synthesized compounds and HDAC2 was observed to be similar to that of MS-275.

Keywords:

Anti-proliferative activity, cancer cell lines, MTT assay, molecular docking stimulation, N-substituted benzamide derivative, SAR studies.

Affiliation:

School of Chemical Engineering, Sichuan University, Chengdu 610065, Sichuan, School of Chemical Engineering, Sichuan University, Chengdu 610065, Sichuan, School of Chemical Engineering, Sichuan University, Chengdu 610065, Sichuan, School of Chemical Engineering, Sichuan University, Chengdu 610065, Sichuan, School of Chemical Engineering, Sichuan University, Chengdu 610065, Sichuan, State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Chengdu 610041, Sichuan, State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Chengdu 610041, Sichuan

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