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

Abstract

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]. Chemical Research in Chinese Universities, 2018, 34(1): 75-83.

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