Design, Synthesis and Biological Evaluation of Novel Selective Thiol-based Histone Deacetylase(HDAC) VI InhibitorsBearing Indeno[1,2-c]pyrazole or Benzoindazole Scaffold

doi:10.1007/s40242-018-7239-6

高等学校化学研究 ›› 2018, Vol. 34 ›› Issue (1): 75-83.doi: 10.1007/s40242-018-7239-6

Design, Synthesis and Biological Evaluation of Novel Selective Thiol-based Histone Deacetylase(HDAC) VI InhibitorsBearing Indeno[1,2-c]pyrazole or Benzoindazole Scaffold

XU Qihao, YU Shujia, CAI Yijun, YANG Jinyu, ZHAO Linxiang, LIU Dan

Key Laboratory of Structure-based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, P. R. China

收稿日期:2017-07-13 出版日期:2018-02-01 发布日期:2018-01-20
通讯作者: LIU Dan,E-mail:sammyld@163.com E-mail:sammyld@163.com
基金资助:
Supported by the National Natural Science Foundation of China(No.81473086) and the Natural Science Foundation of Liaoning Province, China(No.2015020728-301).

Design, Synthesis and Biological Evaluation of Novel Selective Thiol-based Histone Deacetylase(HDAC) VI InhibitorsBearing Indeno[1,2-c]pyrazole or Benzoindazole Scaffold

XU Qihao, YU Shujia, CAI Yijun, YANG Jinyu, ZHAO Linxiang, LIU Dan

Key Laboratory of Structure-based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, P. R. China

Received:2017-07-13 Online:2018-02-01 Published:2018-01-20
Contact: LIU Dan,E-mail:sammyld@163.com E-mail:sammyld@163.com
Supported by:
Supported by the National Natural Science Foundation of China(No.81473086) and the Natural Science Foundation of Liaoning Province, China(No.2015020728-301).

摘要/Abstract

摘要： A series of thiol-based indeno[1,2-c]pyrazoles and benzoindazole compounds was designed and synthesized according to the structural specificity of histone deacetylase VI(HDAC6) and the structural characteristics of HDAC inhibitors. The inhibitory activities of the target compounds against HDAC6 and HDAC1 were screened by fluorescence analysis. Most of the target compounds showed moderate inhibitory activity against HDAC6(IC₅₀=44—598 nmol/L). Among them, compound A-4 displayed the highest selectivity against HDAC6 and similar inhibitory activity(IC₅₀=44 nmol/L) to that of the positive drug SAHA(IC₅₀=41 nmol/L) against HDAC6.

关键词: Histone deacetylase VI(HDAC6) selective inhibitor, Indeno[1, 2-c]pyrazole compound, Benzoindazole compound, Antitumor

Abstract: A series of thiol-based indeno[1,2-c]pyrazoles and benzoindazole compounds was designed and synthesized according to the structural specificity of histone deacetylase VI(HDAC6) and the structural characteristics of HDAC inhibitors. The inhibitory activities of the target compounds against HDAC6 and HDAC1 were screened by fluorescence analysis. Most of the target compounds showed moderate inhibitory activity against HDAC6(IC₅₀=44—598 nmol/L). Among them, compound A-4 displayed the highest selectivity against HDAC6 and similar inhibitory activity(IC₅₀=44 nmol/L) to that of the positive drug SAHA(IC₅₀=41 nmol/L) against HDAC6.

Key words: Histone deacetylase VI(HDAC6) selective inhibitor, Indeno[1,2-c]pyrazole compound, Benzoindazole compound, Antitumor

XU Qihao, YU Shujia, CAI Yijun, YANG Jinyu, ZHAO Linxiang, LIU Dan. Design, Synthesis and Biological Evaluation of Novel Selective Thiol-based Histone Deacetylase(HDAC) VI InhibitorsBearing Indeno[1,2-c]pyrazole or Benzoindazole Scaffold[J]. 高等学校化学研究, 2018, 34(1): 75-83.

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Design, Synthesis and Biological Evaluation of Novel Selective Thiol-based Histone Deacetylase(HDAC) VI InhibitorsBearing Indeno[1,2-c]pyrazole or Benzoindazole Scaffold

Design, Synthesis and Biological Evaluation of Novel Selective Thiol-based Histone Deacetylase(HDAC) VI InhibitorsBearing Indeno[1,2-c]pyrazole or Benzoindazole Scaffold

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