Citation: Zhang Xiangna, He Feng, Zhang Qiuqiong, Lü Jiahui, Xu A'na, Yu Chenggong, Qu Ying, Wu Jingde. Design, Synthesis and Evaluation of Anti-tumor Activities of Chidamide Derivatives[J]. Chinese Journal of Organic Chemistry, ;2019, 39(7): 1983-1989. doi: 10.6023/cjoc201812036 shu

Design, Synthesis and Evaluation of Anti-tumor Activities of Chidamide Derivatives

Key Laboratory of Chemical Biology(Ministry of Education), School of Pharmaceutical Science, Shandong University, Jinan 250012

Corresponding author: Wu Jingde, wujingde70@sdu.edu.cn

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Received Date: 19 December 2018
Revised Date: 12 January 2019
Available Online: 29 July 2019
Fund Project: Project supported by the Key Research and Development Plan of Shandong Province (No. 2017CXGC1401)the Key Research and Development Plan of Shandong Province 2017CXGC1401

Figures(3)

A series of novel chidamide based histone deacetylases (HDACs) inhibitors were rationally designed and synthesized to increase the Zn²⁺ chelating and selectivity. Biological characterization established that most of the compounds showed moderate antiproliferative activitites in cancer cell lines. Among the tested analogs, (E)-N-(4-amino-6- fluoro-[1, 1'-biphenyl]-3-yl)-4-((3-(pyridin-3-yl)acrylamido)methyl)benzamide (7i) and (E)-N-(2-amino-4-fluoro-5-(thiophen- 2-yl)phenyl)-4-((3-(pyridin-3-yl)acrylamido)methyl)benzamide (7j) exhibit the most potent antiproliferative activity with IC₅₀ of 3.29 and 2.59 μmol/L in Jurkat cells, respectively. Furthermore, these two compounds have a certain HDAC inhibitory activity. Collectively, the results partly encourage further development of more potential analogs based on chidamide.
- chidamide,
- HDACs,
- anti-tumor activity,
- benzamide
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