Synthesis, Biological Activity Evaluation and Molecular Modeling Study on the New Isoconessimine Derivatives as Acetylcholinesterase Inhibitors

doi:10.1002/cjoc.201300441

	Synthesis, Biological Activity Evaluation and Molecular Modeling Study on the New Isoconessimine Derivatives as Acetylcholinesterase Inhibitors
	Jin, Guofei 2; Yang, Zhongduo 2; Xue, Weiwei 1; Sheng, Jie 2; Shi, Yin 3; Yao, Xiaojun 1
刊名	CHINESE JOURNAL OF CHEMISTRY
	2013-09
卷号	31 期号:9 页码:1228-1233
关键词	isoconessimine derivatives acetylcholinesterase inhibitors molecular docking
ISSN号	1001-604X
DOI	10.1002/cjoc.201300441
英文摘要	New isoconessimine derivatives were synthesized from conessine (1) and evaluated as acetylcholinesterase (AChE) inhibitors. The derivatives were prepared via two reaction steps, N-demethylation and nucleophilic substitution. All of the synthesized derivatives exhibited more potential anti-acetylcholinesterase activities than conessine (1) (IC50=16 mu molL(-1)) and isoconessimine (2) (IC50>300 mu molL(-1)). Compound 7b (3-[methyl-[2-(4-nitrophenoxy)ethyl]amino]con-5-enine) showed the most potent inhibitory activity with an IC50 of 110 nmol/L which is close to that of reference compound huperzine A (IC50=70 nmol/L). The mode of AChE inhibition by 7b was reversible and non-competitive. In addition, molecular modeling was performed to explore the binding mode of inhibitor 7b at the active site of AChE and the results showed that 7b could be docked into the acetylcholinesterase active site and compound 7b had hydrophobic interactions with Trp279 and Leu282.
资助项目	Key Laboratory of Veterinary Pharmaceutical Development of the Ministry of Agriculture[1610322011011]
WOS研究方向	Chemistry
语种	英语
出版者	WILEY-V C H VERLAG GMBH
WOS记录号	WOS:000327882900015
状态	已发表
内容类型	期刊论文
源URL	[http://119.78.100.223/handle/2XXMBERH/34639]
专题	生命科学与工程学院
通讯作者	Yang, Zhongduo
作者单位	1.Lanzhou Univ, Dept Chem, Lanzhou, Gansu 730000, Peoples R China 2.Lanzhou Univ Technol, Sch Life Sci & Engn, Lanzhou 730050, Gansu, Peoples R China 3.CAAS, Lanzhou Inst Husb & Pharmaceut Sci, Minist Agr, Key Lab New Anim Drug Project,Key Lab Vet Pharm, Lanzhou 730050, Gansu, Peoples R China
推荐引用方式 GB/T 7714	Jin, Guofei,Yang, Zhongduo,Xue, Weiwei,et al. Synthesis, Biological Activity Evaluation and Molecular Modeling Study on the New Isoconessimine Derivatives as Acetylcholinesterase Inhibitors[J]. CHINESE JOURNAL OF CHEMISTRY,2013,31(9):1228-1233.
APA	Jin, Guofei,Yang, Zhongduo,Xue, Weiwei,Sheng, Jie,Shi, Yin,&Yao, Xiaojun.(2013).Synthesis, Biological Activity Evaluation and Molecular Modeling Study on the New Isoconessimine Derivatives as Acetylcholinesterase Inhibitors.CHINESE JOURNAL OF CHEMISTRY,31(9),1228-1233.
MLA	Jin, Guofei,et al."Synthesis, Biological Activity Evaluation and Molecular Modeling Study on the New Isoconessimine Derivatives as Acetylcholinesterase Inhibitors".CHINESE JOURNAL OF CHEMISTRY 31.9(2013):1228-1233.