Design, synthesis and in vitro evaluation of amidoximes as histone deacetylase inhibitors for cancer therapy. Issue 19 (1st October 2016)

• Record Type: Journal Article
• Authors: Jiao, Peifu; Jin, Peng; Li, Chencan; Cui, Lechao; Dong, Lihua; Pan, Bin; Song, Wentong; Ma, Liang; Dong, Jinlong; Song, Lei; Jin, Xinjie; Li, Faming; Wan, Maosheng; Lv, Zhitao; Geng, Qiaohong
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 26:Issue 19(2016)
• Page Start: 4679
• Page End: 4683
• Publication Date: 2016-10-01
• Subjects: Amindoximes -- HDACs -- Cytotoxicity -- G2/M arrest; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2016.08.073
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: Amindoximes are geometric isomers of N -hydroxyamidines which are bioisosteres of hydroxamates. Since amindoxime group is capable of chelating transition metal ions including zinc ion, amindoximes should possess histone deacetylases (HDACs) inhibitory activity. In this work, we designed and synthesized a series of amindoximes, examined their inhibitory activities against HDACs, and investigated their cytotoxicity to human cancer cells. Preliminary results demonstrated that amindoximes possessed submicromolar HDACs inhibitory activity, with noteworthy enhancement compared with hydroxamates. Furthermore, the amindoximes arrested HCT116 and A549 cells in G2/M phase and showed good efficacy in inducing cells death. We provided a proof-of-concept that amindoximes could be used as HDACs inhibitors and hold great promise as epigenetic drugs.