Design, synthesis and biological evaluation of bisthiazole-based trifluoromethyl ketone derivatives as potent HDAC inhibitors with improved cellular efficacy

  • Eur J Med Chem. 2016 Apr 13:112:81-90. doi: 10.1016/j.ejmech.2016.02.003.
Chao-Jun Gong  1 ,  An-Hui Gao  1 ,  Yang-Ming Zhang  1 ,  Ming-Bo Su  1 ,  Fei Chen  1 ,  Li Sheng  1 ,  Yu-Bo Zhou  1 ,  Jing-Ya Li  1 ,  Jia Li  2 ,  Fa-Jun Nan  3
Affiliations
  • 1. Chinese National Center for Drug Screening, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 189 Guoshoujing Road, Zhangjiang Hi-Tech Park, Shanghai, 201203, PR China.
  • 2. Chinese National Center for Drug Screening, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 189 Guoshoujing Road, Zhangjiang Hi-Tech Park, Shanghai, 201203, PR China. Electronic address: [email protected].
  • 3. Chinese National Center for Drug Screening, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 189 Guoshoujing Road, Zhangjiang Hi-Tech Park, Shanghai, 201203, PR China. Electronic address: [email protected].
PMID: 26890114 DOI: 10.1016/j.ejmech.2016.02.003
Abstract

Histone deacetylases (HDACs) are a class of epigenetic modulators with complex functions in histone post-translational modifications and are well known targets for antineoplastic drugs. We have previously developed a series of bisthiazole-based hydroxamic acids as novel potent HDAC inhibitors. In the present work, a new series of bisthiazole-based compounds with different zinc binding groups (ZBGs) have been designed and synthesized. Among them is compound 7, containing a trifluoromethyl ketone as the ZBG, which displays potent inhibitory activity towards human HDACs and improved antiproliferative activity in several Cancer cell lines.

Keywords
Bisthiazole; Histone deacetylases; Trifluoromethyl ketones; ZBG.