Design, synthesis and biological evaluation of LX2343 derivatives as neuroprotective agents for the treatment of Alzheimer's disease

doi:10.1016/j.ejmech.2017.12.080

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	Design, synthesis and biological evaluation of LX2343 derivatives as neuroprotective agents for the treatment of Alzheimer's disease
	Sun, Guanglong 1,2,3; Wang, Junwei 3; Guo, Xiaodan 1,2; Lei, Min1,2 ; Zhang, Yinan 3; Wang, Xiachang 3; Shen, Xu3 ; Hu, Lihong 1,2,3
刊名	EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
	2018-02-10
卷号	145 页码:622-633
关键词	LX2343 derivatives Neuroprotective agents Alzheimer's disease Structural modifications Structure-activity relationships
ISSN号	0223-5234
DOI	10.1016/j.ejmech.2017.12.080
文献子类	Article
英文摘要	A series of LX2343 derivatives were designed, synthesized and evaluated as neuroprotective agents for Alzheimer's disease (AD) in vitro. Most of the compounds displayed potent neuroprotective activities. Especially for compound A6, exhibited a remarkable EC50 value of 0.22 mu M. Further investigation demonstrated that compound A6 can significantly reduce A beta production and increase A beta clearance, and alleviate Tau hyperphosphorylation. Most importantly, compound A6 could ameliorate learning and memory impairments in APP/PS1 transgenic mice. The present study evidently showed that compound A6 is a potent neuroprotective agent and might serve as a promising lead candidate for the treatment of Alzheimer's disease. (C) 2018 Elsevier Masson SAS. All rights reserved.
资助项目	National Natural Science Foundation of China[81473110] ; National Natural Science Foundation of China[81773596] ; National Natural Science Foundation of China[81561148011] ; Natural Science Foundation of Jiangsu Higher Education Institutions[17KJA360004] ; Program for Outstanding Scientific and Technological Innovation Team of Jiangsu Higher Education Institutions[00000000] ; Priority Academic Program Development of Jiangsu Higher Education Institutions[00000000]
WOS关键词	OXIDATIVE STRESS ; GSK-3-BETA INHIBITORS ; SH-SY5Y CELLS ; APOPTOSIS ; POTENT ; MODEL ; HYPOTHESIS ; DEMENTIAS
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:000425198200048
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/279908]
专题	上海中药现代化研究中心中科院受体结构与功能重点实验室新药研究国家重点实验室
通讯作者	Shen, Xu; Hu, Lihong
作者单位	1.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China; 3.Nanjing Univ Chinese Med, Stake Key Lab Cultivat Base TCM Qual & Efficacy, Jiangsu Collaborat Innovat Ctr Chinese Med Resour, Jiangsu Key Lab Funct Subst Chinese Med,Sch Pharm, Nanjing 210023, Jiangsu, Peoples R China;
推荐引用方式 GB/T 7714	Sun, Guanglong,Wang, Junwei,Guo, Xiaodan,et al. Design, synthesis and biological evaluation of LX2343 derivatives as neuroprotective agents for the treatment of Alzheimer's disease[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2018,145:622-633.
APA	Sun, Guanglong.,Wang, Junwei.,Guo, Xiaodan.,Lei, Min.,Zhang, Yinan.,...&Hu, Lihong.(2018).Design, synthesis and biological evaluation of LX2343 derivatives as neuroprotective agents for the treatment of Alzheimer's disease.EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,145,622-633.
MLA	Sun, Guanglong,et al."Design, synthesis and biological evaluation of LX2343 derivatives as neuroprotective agents for the treatment of Alzheimer's disease".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 145(2018):622-633.