2. Academic Validation
  3. Synthesis and biological study of class I selective HDAC inhibitors with NO releasing activity

Synthesis and biological study of class I selective HDAC inhibitors with NO releasing activity

  • Bioorg Chem. 2020 Nov;104:104235. doi: 10.1016/j.bioorg.2020.104235.
Qin'ge Ding 1,  Chunxi Liu 2,  Chunlong Zhao 1,  Hang Dong 1,  Qifu Xu 1,  C James Chou 3,  Yingjie Zhang 4
Affiliations

Affiliations

  • 1 Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 44 West Wenhua Road, Ji'nan, Shandong 250012, PR China.
  • 2 Department of Pharmacy, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Ji'nan, Shandong 250012, PR China.
  • 3 Department of Drug Discovery and Biomedical Sciences, South Carolina College of Pharmacy, Medical University of South Carolina, Charleston, SC 29425, United States.
  • 4 Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 44 West Wenhua Road, Ji'nan, Shandong 250012, PR China. Electronic address: zhangyingjie@sdu.edu.cn.
PMID: 32896808 DOI: 10.1016/j.bioorg.2020.104235
Abstract

Based on the multi-mechanism antitumor strategy and the regulatory effect of nitric oxide (NO) on histone deacetylases (HDACs), a series of N-acyl-o-phenylenediamine-based HDAC inhibitors equipped with the phenylsulfonylfuroxan module as NO donor was designed, synthesized and biologically evaluated. The in vitro HDAC inhibitory assays revealed that compared with the clinical class I selective HDAC Inhibitor MS275, compounds 7c, 7d and 7e possessed similar HDAC inhibitory potency and selective profile, which were confirmed by the results of western blot analysis. The western blot analysis also showed that NO scavenger N-acetyl cysteine (NAC) could weaken the intracellular HDAC inhibitory ability of compound 7c, supporting the HDAC inhibitory effect of NO generated by 7c. It is worth noting that compounds 7c, 7d and 7e exhibited more potent in vitro antiproliferative activities than MS275 against all four tested solid tumor cell lines. The promising in vivo antitumor potency of 7c was demonstrated in a HCT116 xenograft model.

Keywords

Anticancer; Histone deacetylase; Hybrid; N-acyl-o-phenylenediamine; Nitric oxide; Phenylsulfonylfuroxan.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-147840
    HDAC Inhibitor