Design, synthesis and biological evaluation of novel selective thiol-based histone deacetylase(HDAC) VI inhibitors bearing indeno[1,2-c]pyrazole or benzoindazole scaffold

Qihao Xu; Shujia Yu; Yijun Cai; Jinyu Yang; Linxiang Zhao; Dan Liu

doi:10.1007/s40242-018-7239-6

Chemical Research in Chinese Universities ›› 2018, Vol. 34 ›› Issue (1) : 75 -83. DOI: 10.1007/s40242-018-7239-6

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Design, synthesis and biological evaluation of novel selective thiol-based histone deacetylase(HDAC) VI inhibitors bearing indeno[1,2-c]pyrazole or benzoindazole scaffold

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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.

Keywords

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

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Qihao Xu, Shujia Yu, Yijun Cai, Jinyu Yang, Linxiang Zhao, Dan Liu. Design, synthesis and biological evaluation of novel selective thiol-based histone deacetylase(HDAC) VI inhibitors bearing indeno[1,2-c]pyrazole or benzoindazole scaffold. Chemical Research in Chinese Universities, 2018, 34(1): 75-83 DOI:10.1007/s40242-018-7239-6

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