2. Academic Validation
  3. Design, synthesis and anti-tumor activity study of novel histone deacetylase inhibitors containing isatin-based caps and o-phenylenediamine-based zinc binding groups

Design, synthesis and anti-tumor activity study of novel histone deacetylase inhibitors containing isatin-based caps and o-phenylenediamine-based zinc binding groups

  • Bioorg Med Chem. 2017 Jun 15;25(12):2981-2994. doi: 10.1016/j.bmc.2017.03.036.
Shuai Gao 1,  Jie Zang 1,  Qianwen Gao 1,  Xuewu Liang 1,  Qinge Ding 1,  Xiaoyang Li 2,  Wenfang Xu 1,  C James Chou 2,  Yingjie Zhang 3
Affiliations

Affiliations

  • 1 Department of Medicinal Chemistry, School of Pharmacy, Shandong University, 44 West Culture Road, 250012 Ji'nan, Shandong, PR China.
  • 2 Department of Drug Discovery and Biomedical Sciences, South Carolina College of Pharmacy, Medical University of South Carolina, Charleston, South Carolina 29425, United States.
  • 3 Department of Medicinal Chemistry, School of Pharmacy, Shandong University, 44 West Culture Road, 250012 Ji'nan, Shandong, PR China; Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Jinan, Shandong 250012, Peoples' Republic of China. Electronic address: zhangyingjie@sdu.edu.cn.
PMID: 28511906 DOI: 10.1016/j.bmc.2017.03.036
Abstract

As a hot topic of epigenetic studies, histone deacetylases (HDACs) are related to lots of diseases, especially Cancer. Further researches indicated that different HDAC isoforms played various roles in a wide range of tumor types. Herein a novel series of HDAC inhibitors with isatin-based caps and o-phenylenediamine-based zinc binding groups have been designed and synthesized through scaffold hopping strategy. Among these compounds, the most potent compound 9n exhibited similar if not better HDAC inhibition and antiproliferative activities against multiple tumor cell lines compared with the positive control entinostat (MS-275). Additionally, compared with MS-275 (IC50 values for HDAC1, 2 and 3 were 0.163, 0.396 and 0.605µM, respectively), compound 9n with IC50 values of 0.032, 0.256 and 0.311µM for HDAC1, 2 and 3 respectively, showed a moderate HDAC1 selectivity.

Keywords

Anticancer; Epigenetics; HDAC inhibitors; Isatin.

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