Synthesis and structure-activity relationship of nuciferine derivatives as potential acetylcholinesterase inhibitors

doi:10.1007/s00044-013-0905-9

	Synthesis and structure-activity relationship of nuciferine derivatives as potential acetylcholinesterase inhibitors
	Yang, Zhongduo 1; Song, Zhuwen 1; Xue, Weiwei 2; Sheng, Jie 1; Shu, Zongmei 1; Shi, Yin 3; Liang, Jibei 1; Yao, Xiaojun 2
刊名	MEDICINAL CHEMISTRY RESEARCH
	2014-06
卷号	23 期号:6 页码:3178-3186
关键词	Aporphine alkaloids Acetylcholinesterase inhibitors Structure-activity relationships
ISSN号	1054-2523
DOI	10.1007/s00044-013-0905-9
英文摘要	Acetylcholinesterase inhibitors (AChEIs) are currently the best available pharmacotherapy for Alzheimer patients, but because of bioavailability issues, there is still great interest in discovering better AChEIs. The aporphine alkaloid is an important class of natural products, which shows diverse biological activity, such as acetylcholinesterase inhibitory activity. To find new lead AChEIs compounds, eight aporphine alkaloids were synthesized by O-dealkylation, N-dealkylation, and ring aromatization reactions using nuciferine as raw material. The anti-acetylcholinesterase activity of synthesized compounds was measured using modified Ellman's method. The results showed that some synthesized compounds exhibited higher affinity to AChE than the parent compound nuciferine. Among these compounds, 1,2-dihydroxyaporphine (2) and dehydronuciferine (5) were the most active compounds (IC50 = 28 and 25 mu g/mL, respectively). Preliminary analysis of structure-activity relationships suggested that aromatization of the C ring, the presence of the alkoxyl group at C1 and the hydroxy group at C2 position as well as the alkyl substituent at the N atom were favorable to the acetylcholinesterase inhibition. Molecular docking was also applied to predict the binding modes of compounds 1, 2, and 9 into the huperzine A binding site of AChE.
资助项目	Zhejiang Provincial Natural Science Foundation of China[LY12B02005]
WOS研究方向	Pharmacology & Pharmacy
语种	英语
出版者	SPRINGER BIRKHAUSER
WOS记录号	WOS:000334184400043
状态	已发表
内容类型	期刊论文
源URL	[http://119.78.100.223/handle/2XXMBERH/34373]
专题	生命科学与工程学院
通讯作者	Yang, Zhongduo
作者单位	1.Lanzhou Univ Technol, Sch Life Sci & Engn, Lanzhou 730050, Gansu, Peoples R China 2.Lanzhou Univ, Dept Chem, Lanzhou 730000, Peoples R China 3.CAAS, Key Lab New Anim Drug Project, Key Lab Vet Pharmaceut Dev, Minist Agr,Lanzhou Inst Husb & Pharmaceut Sci, Lanzhou 730050, Gansu, Peoples R China
推荐引用方式 GB/T 7714	Yang, Zhongduo,Song, Zhuwen,Xue, Weiwei,et al. Synthesis and structure-activity relationship of nuciferine derivatives as potential acetylcholinesterase inhibitors[J]. MEDICINAL CHEMISTRY RESEARCH,2014,23(6):3178-3186.
APA	Yang, Zhongduo.,Song, Zhuwen.,Xue, Weiwei.,Sheng, Jie.,Shu, Zongmei.,...&Yao, Xiaojun.(2014).Synthesis and structure-activity relationship of nuciferine derivatives as potential acetylcholinesterase inhibitors.MEDICINAL CHEMISTRY RESEARCH,23(6),3178-3186.
MLA	Yang, Zhongduo,et al."Synthesis and structure-activity relationship of nuciferine derivatives as potential acetylcholinesterase inhibitors".MEDICINAL CHEMISTRY RESEARCH 23.6(2014):3178-3186.