2. Academic Validation
  3. Synthesis and in Vitro and in Vivo Biological Evaluation of Tissue-Specific Bisthiazole Histone Deacetylase (HDAC) Inhibitors

Synthesis and in Vitro and in Vivo Biological Evaluation of Tissue-Specific Bisthiazole Histone Deacetylase (HDAC) Inhibitors

  • J Med Chem. 2020 Jan 23;63(2):804-815. doi: 10.1021/acs.jmedchem.9b01792.
Shu-Wei Zhang 1 2,  Chao-Jun Gong 1,  Ming-Bo Su 1,  Fei Chen 1,  Ting He 3,  Yang-Ming Zhang 1 4,  Qian-Qian Shen 3,  Yi Su 3,  Jian Ding 3,  Jia Li 1,  Yi Chen 3,  Fa-Jun Nan 1 4
Affiliations

Affiliations

  • 1 State Key Laboratory of Drug Research, the National Center for Drug Screening , Shanghai Institute of Materia Medica, Chinese Academy of Sciences , Shanghai , 201203 , China.
  • 2 University of Chinese Academy of Sciences , No. 19A Yuquan Road , Beijing 100049 , P. R. China.
  • 3 Division of Antitumor Pharmacology, State Key Laboratory of Drug Research , Shanghai Institute of Materia Medica, Chinese Academy of Sciences , Shanghai 201203 , China.
  • 4 Yantai Key Laboratory of Nanomedicine & Advanced Preparations , Yantai Institute of Materia Medica , Shandong 264000 , China.
PMID: 31855601 DOI: 10.1021/acs.jmedchem.9b01792
Abstract

A series of bisthiazole-based hydroxamic acids as novel potent HDAC inhibitors was developed during our previous work. In the present work, a new series of highly potent bisthiazole-based compounds were designed and synthesized. Among the prepared compounds, compound H13, which contains an α-(S)-methyl-substituted benzyl group, displays potent inhibitory activity toward human HDACs and several Cancer cells lines. Compound H13 has a favorable PK profile and high tissue distribution specificity in the colon, as well as good efficacy in the AOM-DSS mouse model for colitis-associated colonic tumorigenesis.

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