Discovery of Tryptophan-tetrahydroisoquinoline Derivatives as Multifunctional Agents for Treatment of Alzheimer's Disease  

作　　者：Xin Lu Yijun Liu Nan Qin Chenxi Du Yanyu Hu Yao Chen Haopeng Sun 

机构地区：[1]School of Pharmacy,China Pharmaceutical University,Nanjing,Jiangsu 211198,China [2]School of Pharmacy,Nanjing University of Chinese Medicine,Nanjing,Jiangsu 210023,China [3]Department of Natural Medicinal Chemistry,China Pharmaceutical University,Nanjing,Jiangsu 211198,China

出　　处：《Chinese Journal of Chemistry》2022年第15期1821-1830,共10页中国化学（英文版）

基　　金：We gratefully thank the support from the grants of the National Natural Science Foundation of China(Nos.81872728 and 82173652);the Natural Science Foundation of Jiangsu Province(No.BK20191411).

摘　　要：Comprehensive Summary The cholinesterases are essential targets implicated in the pathogenesis of Alzheimer's disease(AD).We have identified tryptophan-tetrahydroisoquinoline derivatives as selective micro-nanomolar butyrylcholinesterase(BChE)inhibitors.Molecular docking was applied for the rational design and binding mode analysis.They were defined according to their target inhibitory activity,low cytotoxicity,predicted permeability through the blood-brain barrier(BBB),and in vivo cognitive improvement.Additionally,the preferred compound showed ability to decrease self-induced Aβ1-42 aggregation and Aβ1-42 induced SH-SY5Y cell injury.Altogether,these factors indicated their potential as unique lead compounds for AD treatment.

关 键 词：Alzheimer's disease BUTYRYLCHOLINESTERASE INHIBITORS Molecular modeling Biological activity 

分 类 号：R749.16[医药卫生—神经病学与精神病学]