Development of chalcone-O-alkylamine derivatives as multifunctional agents against Alzheimer's disease

doi:10.1016/j.ejmech.2019.111737

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	Development of chalcone-O-alkylamine derivatives as multifunctional agents against Alzheimer's disease
	Bai, Ping 1,4; Wang, Keren 3; Zhang, Pengfei 2; Shi, Jian 3; Cheng, Xinfeng 3; Zhang, Qi 4; Zheng, Cheng 4; Cheng, Yao 4; Yang, Jian 4; Lu, Xiaoxia 4
刊名	EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
	2019
卷号	183 页码:111737
关键词	Alzheimer's disease Chalcone-O-Alkylamine derivatives Multi-functional agents Rational design Synthesis Precognitive effect
ISSN号	0223-5234
DOI	10.1016/j.ejmech.2019.111737
产权排序	1
文献子类	Article
英文摘要	A series of novel chalcone-O-alkylamine derivatives were designed, synthesized and evaluated as multifunctional anti-Alzheimer's disease agents. Based on the experimental results, compound 23c exhibited good inhibitory potency on both acetylcholinesterase (IC50 = 1.3 +/- 0.01 mu M) and butyrylcholinesterase (IC50 = 1.2 +/- 0.09 mu M). Besides, 23c exhibited selective MAO-B inhibitory activity with IC50 value of 0.57 +/- 0.01 mu M. Compound 23c was also a potential antioxidant and neuroprotectant. In addition, compound 23c could inhibit self-induced A beta(1-42) aggregation. Moreover, compound 23c was a selective metal chelator, and could inhibit and disaggregate Cu2+-induced A beta(1-42) aggregation, which was supported by the further transmission electron microscopy images. Furthermore, 23c could cross the blood-brain barrier in vitro, and improved scopolamine-induced memory impairment in vivo assay. Molecular modeling studies showed that 23c could bind to the active site of AChE, BuChE, A beta(1-42) and MAO-B. Taken together, these results suggested that compound 23c might be a potential multifunctional agent for the treatment of AD. (C) 2019 Elsevier Masson SAS. All rights reserved.
学科主题	Chemistry & Analysis
URL标识	查看原文
WOS关键词	MANNICH BASE DERIVATIVES ; TARGET-DIRECTED LIGANDS ; DRUG DESIGN STRATEGY ; NEUROPROTECTIVE PROPERTIES ; AGGREGATION INHIBITORS ; BETA AGGREGATION ; ACETYLCHOLINESTERASE ; ANTIOXIDANT ; HYBRIDS ; PLAQUES
WOS研究方向	Pharmacology & Pharmacy
语种	英语
出版者	ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
WOS记录号	WOS:000498308700063
内容类型	期刊论文
源URL	[http://210.75.237.14/handle/351003/30977]
专题	国家天然药物工程技术研究中心_天然产物研究
作者单位	1.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 2.Henan Univ Minsheng Coll, Sch Med, Kaifeng 475000, Peoples R China; 3.Nanyang Normal Univ, Coll Chem & Pharmaceut Engn, Nanyang 473061, Peoples R China; 4.Chinese Acad Sci, Chengdu Inst Biol, Chengdu 610041, Sichuan, Peoples R China;
推荐引用方式 GB/T 7714	Bai, Ping,Wang, Keren,Zhang, Pengfei,et al. Development of chalcone-O-alkylamine derivatives as multifunctional agents against Alzheimer's disease[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2019,183:111737.
APA	Bai, Ping.,Wang, Keren.,Zhang, Pengfei.,Shi, Jian.,Cheng, Xinfeng.,...&Sang, Zhipei.(2019).Development of chalcone-O-alkylamine derivatives as multifunctional agents against Alzheimer's disease.EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,183,111737.
MLA	Bai, Ping,et al."Development of chalcone-O-alkylamine derivatives as multifunctional agents against Alzheimer's disease".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 183(2019):111737.