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

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• 作者：Peifu Jiao^a ; Peng Jin^a ; Chencan Li^a ; Lechao Cui^a ; Lihua Dong^a ; Bin Pan^c ; Wentong Song^c ; Liang Ma^c ; Jinlong Dong^a ; Lei Song^a ; Xinjie Jin^a ; Faming Li^a ; Maosheng Wan^b ; ^{shmw11258@163.com" class="auth_mail" title="E-mail the corresponding author} ; Zhitao Lv^c ; ^{rorry-1@163.com" class="auth_mail" title="E-mail the corresponding author} ; Qiaohong Geng^a ; ^{gengqh2006@163.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Amindoximes ; HDACs ; Cytotoxicity ; G2/M arrest
• 刊名：Bioorganic & Medicinal Chemistry Letters
• 出版年：2016
• 出版时间：1 October 2016
• 年：2016
• 卷：26
• 期：19
• 页码：4679-4683
• 全文大小：890 K

文摘

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.