2. Academic Validation
  3. Design, synthesis and in vitro evaluation of amidoximes as histone deacetylase inhibitors for cancer therapy

Design, synthesis and in vitro evaluation of amidoximes as histone deacetylase inhibitors for cancer therapy

  • Bioorg Med Chem Lett. 2016 Oct 1;26(19):4679-4683. doi: 10.1016/j.bmcl.2016.08.073.
Peifu Jiao 1,  Peng Jin 1,  Chencan Li 1,  Lechao Cui 1,  Lihua Dong 1,  Bin Pan 2,  Wentong Song 2,  Liang Ma 2,  Jinlong Dong 1,  Lei Song 1,  Xinjie Jin 1,  Faming Li 1,  Maosheng Wan 3,  Zhitao Lv 4,  Qiaohong Geng 5
Affiliations

Affiliations

  • 1 Department of Chemistry, Qilu Normal University, Jinan, Shandong 250200, China.
  • 2 Shandong Chengchuang Pharmaceutical R&D Co., Ltd, Jinan, Shandong 250101, China.
  • 3 School of Chemistry and Biological Engineering, Hezhou University, Hezhou, Guangxi 542899, China. Electronic address: shmw11258@163.com.
  • 4 Shandong Chengchuang Pharmaceutical R&D Co., Ltd, Jinan, Shandong 250101, China. Electronic address: rorry-1@163.com.
  • 5 Department of Chemistry, Qilu Normal University, Jinan, Shandong 250200, China. Electronic address: gengqh2006@163.com.
PMID: 27597246 DOI: 10.1016/j.bmcl.2016.08.073
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.

Keywords

Amindoximes; Cytotoxicity; G2/M arrest; HDACs.

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