2. Academic Validation
  3. Design, synthesis, and biological evaluation of 1, 3-disubstituted-pyrazole derivatives as new class I and IIb histone deacetylase inhibitors

Design, synthesis, and biological evaluation of 1, 3-disubstituted-pyrazole derivatives as new class I and IIb histone deacetylase inhibitors

  • Eur J Med Chem. 2014 Oct 30:86:639-52. doi: 10.1016/j.ejmech.2014.09.024.
Yiwu Yao 1,  Chenzhong Liao 2,  Zheng Li 3,  Zhen Wang 1,  Qiao Sun 1,  Chunping Liu 1,  Yang Yang 2,  Zhengchao Tu 4,  Sheng Jiang 5
Affiliations

Affiliations

  • 1 Laboratory of Medicinal Chemistry, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.
  • 2 School of Medical Engineering, Hefei University of Technology, Hefei, Anhui 230009, China.
  • 3 The Methodist Hospital Research Institute, Houston, TX 77030, USA.
  • 4 Laboratory of Medicinal Chemistry, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China. Electronic address: tu_zhengchao@gibh.ac.cn.
  • 5 Laboratory of Medicinal Chemistry, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China. Electronic address: jiang_sheng@gibh.ac.cn.
PMID: 25218912 DOI: 10.1016/j.ejmech.2014.09.024
Abstract

A novel series of HDAC inhibitors demonstrating class I and IIb subtype selectivity have been identified using a scaffold-hopping strategy. Several designed compounds showed better selectivity for class I and IIb over class IIa HDAC isoforms comparing to the FDA approved HDAC targeting drug SAHA. A representative lead compound 22 bearing a biphenyl moiety demonstrated promising class I and IIb HDAC isoforms selectivity and in vitro Anticancer activities against several Cancer cell lines. This work could serve as a fundamental platform for further exploration of selective HDAC inhibitors using designed molecular scaffold.

Keywords

HDAC; Isoforms selectivity; Scaffold-hopping; Structure–activity relationship.

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