Synthesis, biological evaluation and molecular modeling of substituted 2-aminobenzimidazoles as novel inhibitors of acetylcholinesterase and butyrylcholinesterase

doi:10.1016/j.bmc.2013.05.001

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	Synthesis, biological evaluation and molecular modeling of substituted 2-aminobenzimidazoles as novel inhibitors of acetylcholinesterase and butyrylcholinesterase
	Zhu, Jinmei 1,2; Wu, Chun-Feng 3; Li, Xiaobing 1,2; Wu, Gui-Sheng4,5 ; Xie, Shan 1,2; Hu, Qian-Nan 1,2; Deng, Zixin 1,2; Zhu, Michael X.6; Luo, Huai-Rong3 ; Hong, Xuechuan 1,2
刊名	BIOORGANIC & MEDICINAL CHEMISTRY
	2013-07-15
卷号	21 期号:14 页码:4218-4224
关键词	Alzheimer's Disease Acetylcholinesterase Butyrylcholinesterase Molecular Modeling 2-aminobenzimidazole
ISSN号	0968-0896
DOI	10.1016/j.bmc.2013.05.001
通讯作者	Zhu, MX (reprint author), Univ Texas Hlth Sci Ctr Houston, Dept Integrat Biol & Pharmacol, Houston, TX 77030 USA. ; Michael.X.Zhu@uth.tmc.edu ; luohuairong@mail.kib.ac.cn ; xhy78@whu.edu.cn
文献子类	Article
英文摘要	A series of novel 2-aminobenzimidazole derivatives were synthesized under microwave irradiation. Their biological activities were evaluated on acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). A number of the 2-aminobenzimidazole derivatives showed good inhibitory activities to AChE and BuChE. Among them, compounds 9, 12 and 13 were found to be >25-fold more selective for BuChE than AChE. No evidence of cytotoxicity was observed by MTT assay in PC12 cells or HepG2 cells exposed to 100 mu M of the compounds. Molecular modeling studies indicate that the benzimidazole moiety of compounds 9, 12 and 13 forms a face-to-face pi-pi stacking interaction in a 'sandwich' form with the indole ring of Trp82 (4.09 angstrom) in the active gorge, and compounds 12 and 13 form a hydrogen bond with His438 at the catalytic site of BuChE. In addition, compounds 12 and 13 fit well into the hydrophobic pocket formed by Ala328, Trp430 and Tyr332 of BuChE. Our data suggest the 2-aminobenzimidazole drugs as promising new selective inhibitors for AChE and BuChE, potentially useful to treat neurodegenerative diseases. (C) 2013 Elsevier Ltd. All rights reserved.
学科主题	Biochemistry & Molecular Biology ; Chemistry, Medicinal ; Chemistry, Organic
WOS关键词	ALZHEIMERS-DISEASE ; DESIGN ; DERIVATIVES ; DONEPEZIL ; DEMENTIA ; ASSAY
WOS研究方向	Biochemistry & Molecular Biology ; Pharmacology & Pharmacy ; Chemistry
语种	英语
WOS记录号	WOS:000320838200028
资助机构	Ministry of Science and Technology of China [2012ZX10004801-003-011]; Chinese Ministry of Education [313040]; Specialized Research Fund of the Doctoral Program of Higher Education [20110141120017]; Fundamental Research Funds for the Central Universities [2012306020201]; National Mega Project on Major Drug Development [2011ZX09401-302]; Yunnan provincial government [20080A007, 2012FB181]; State Key Laboratory of Phytochemistry and Plant Resources in West China [P2008-ZZ21, T2009-KF05, P2010-KF10] ; Ministry of Science and Technology of China(2012ZX10004801-003-011) ; Chinese Ministry of Education(313040) ; Specialized Research Fund of the Doctoral Program of Higher Education(20110141120017) ; Fundamental Research Funds for the Central Universities(2012306020201) ; National Mega Project on Major Drug Development(2011ZX09401-302) ; Yunnan provincial government(20080A007 ; State Key Laboratory of Phytochemistry and Plant Resources in West China(P2008-ZZ21 ; 2012FB181) ; T2009-KF05 ; P2010-KF10)
公开日期	2013-10-16
内容类型	期刊论文
源URL	[http://ir.kib.ac.cn:8080/handle/151853/16739]
专题	昆明植物研究所_植物化学与西部植物资源持续利用国家重点实验室
作者单位	1.Wuhan Univ, Minist Educ, Key Lab Combinatorial Biosynth & Drug Discovery, Wuhan 430071, Peoples R China 2.Wuhan Univ, Sch Pharmaceut Sci, Wuhan 430071, Peoples R China 3.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources West Ch, Kunming 650201, Yunnan, Peoples R China 4.Chinese Acad Sci, Key Lab Anim Models & Human Dis Mech, Kunming 650223, Yunnan, Peoples R China 5.Kunming Inst Zool, Kunming 650223, Yunnan, Peoples R China 6.Univ Texas Hlth Sci Ctr Houston, Dept Integrat Biol & Pharmacol, Houston, TX 77030 USA
推荐引用方式 GB/T 7714	Zhu, Jinmei,Wu, Chun-Feng,Li, Xiaobing,et al. Synthesis, biological evaluation and molecular modeling of substituted 2-aminobenzimidazoles as novel inhibitors of acetylcholinesterase and butyrylcholinesterase[J]. BIOORGANIC & MEDICINAL CHEMISTRY,2013,21(14):4218-4224.
APA	Zhu, Jinmei.,Wu, Chun-Feng.,Li, Xiaobing.,Wu, Gui-Sheng.,Xie, Shan.,...&Hong, Xuechuan.(2013).Synthesis, biological evaluation and molecular modeling of substituted 2-aminobenzimidazoles as novel inhibitors of acetylcholinesterase and butyrylcholinesterase.BIOORGANIC & MEDICINAL CHEMISTRY,21(14),4218-4224.
MLA	Zhu, Jinmei,et al."Synthesis, biological evaluation and molecular modeling of substituted 2-aminobenzimidazoles as novel inhibitors of acetylcholinesterase and butyrylcholinesterase".BIOORGANIC & MEDICINAL CHEMISTRY 21.14(2013):4218-4224.