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

Author(s): Taiping Chen, Hongwu Jiang, Jianjun Zhou, Zicheng Li*, Wencai Huang, Youfu Luo, Yinglan Zhao.

Journal Name: Medicinal Chemistry

Volume 16 , Issue 4 , 2020

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Graphical 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.

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Article Details

Year: 2020
Page: [555 - 562]
Pages: 8
DOI: 10.2174/1573406415666190712120611
Price: $65

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