Design, synthesis and in vitro evaluation of amidoximes as histone deacetylase inhibitors for cancer therapy.
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.
Department of Chemistry, Qilu Normal University, Jinan, Shandong 250200, China.
Peifu
P
Jiao
Department of Chemistry, Qilu Normal University, Jinan, Shandong 250200, China.
Peng
P
Jin
Department of Chemistry, Qilu Normal University, Jinan, Shandong 250200, China.
Chencan
C
Li
Department of Chemistry, Qilu Normal University, Jinan, Shandong 250200, China.
Lechao
L
Cui
Department of Chemistry, Qilu Normal University, Jinan, Shandong 250200, China.
Lihua
L
Dong
Shandong Chengchuang Pharmaceutical R&D Co., Ltd, Jinan, Shandong 250101, China.
Bin
B
Pan
Shandong Chengchuang Pharmaceutical R&D Co., Ltd, Jinan, Shandong 250101, China.
Wentong
W
Song
Shandong Chengchuang Pharmaceutical R&D Co., Ltd, Jinan, Shandong 250101, China.
Liang
L
Ma
Department of Chemistry, Qilu Normal University, Jinan, Shandong 250200, China.
Jinlong
J
Dong
Department of Chemistry, Qilu Normal University, Jinan, Shandong 250200, China.
Lei
L
Song
Department of Chemistry, Qilu Normal University, Jinan, Shandong 250200, China.
Xinjie
X
Jin
Department of Chemistry, Qilu Normal University, Jinan, Shandong 250200, China.
Faming
F
Li
School of Chemistry and Biological Engineering, Hezhou University, Hezhou, Guangxi 542899, China. Electronic address: shmw11258@163.com.
Maosheng
M
Wan
Shandong Chengchuang Pharmaceutical R&D Co., Ltd, Jinan, Shandong 250101, China. Electronic address: rorry-1@163.com.
Zhitao
Z
Lv
Department of Chemistry, Qilu Normal University, Jinan, Shandong 250200, China. Electronic address: gengqh2006@163.com.
Qiaohong
Q
Geng
D056572:Histone Deacetylase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D009369:Neoplasms / Q000188:drug therapy*; D010091:Oximes / Q000737:chemistry / Q000494:pharmacology*
D056572:Histone Deacetylase Inhibitors; D010091:Oximes; C000608634:amidoxime
Amindoximes; Cytotoxicity; G2/M arrest; HDACs