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

doi:10.6023/cjoc201812036

Chin. J. Org. Chem. ›› 2019, Vol. 39 ›› Issue (7): 1983-1989.DOI: 10.6023/cjoc201812036 Previous Articles Next Articles

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西达本胺衍生物的设计合成及抗肿瘤活性评价

张祥娜, 何峰, 张秋琼, 吕佳徽, 徐阿娜, 虞成功, 曲颖, 吴敬德

山东大学药学院化学生物学教育部重点实验室济南 250012

收稿日期:2018-12-19 修回日期:2019-01-12 发布日期:2019-03-29
通讯作者: 吴敬德 E-mail:wujingde70@sdu.edu.cn
基金资助:
山东省重点研发计划（No.2017CXGC1401）资助项目.

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

Zhang Xiangna, He Feng, Zhang Qiuqiong, Lü Jiahui, Xu A'na, Yu Chenggong, Qu Ying, Wu Jingde

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

Received:2018-12-19 Revised:2019-01-12 Published:2019-03-29
Contact: 10.6023/cjoc201812036 E-mail:wujingde70@sdu.edu.cn
Supported by:
Project supported by the Key Research and Development Plan of Shandong Province (No. 2017CXGC1401).

1. Design, Synthesis and Evaluation of Anti-tumor Activities of Chidamide Derivatives.PDF(2196KB)

Abstract

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.

Key words: chidamide, HDACs, anti-tumor activity, benzamide

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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]. Chin. J. Org. Chem., 2019, 39(7): 1983-1989.

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西达本胺衍生物的设计合成及抗肿瘤活性评价

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

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