Synthesis and biological evaluation of novel histone deacetylases inhibitors with nitric oxide releasing activity. Issue 15 (1st August 2015)

• Record Type: Journal Article
• Authors: Duan, Wenwen; Hou, Jinning; Chu, Xiaojing; Li, Xiaoqian; Zhang, Jian; Li, Jin; Xu, Wenfang; Zhang, Yingjie
• Is Part Of: Bioorganic & medicinal chemistry. Volume 23:Issue 15(2015)
• Page Start: 4481
• Page End: 4488
• Publication Date: 2015-08-01
• Subjects: HDAC inhibitor -- Nitric oxide -- Benzofuroxan -- Multifunctional drugs -- Epigenetic; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2015.06.015
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Abstract: A novel series of histone deacetylases inhibitors (HDACIs) containing benzofuroxan pharmacophore as nitric oxide (NO) donor were designed based on the combination principle and 'multifunctional drugs' theory. As a novel study on embedding NO donor into the structure of HDACIs, all designed hybrid compounds, especially 19d and 24d, displayed remarkable HDACs inhibitory activity and outstanding antiproliferative activity on tumor cells. Besides, they could produce high levels of NO in HCT-116 cells; furthermore, their antiproliferative activity on HCT-116 cells could be diminished by pretreatment with hemoglobin, as the NO scavenger, in a dose-dependent manner. All in all, our designed compounds displayed great inhibitory activities and might offer a prospective avenue to discover novel anti-cancer drugs.