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

被引：5
|
作者：
Lu, Xin [1 ]
Liu, Yijun [1 ]
Qin, Nan [3 ]
Du, Chenxi [1 ]
Hu, Yanyu [3 ]
Chen, Yao [2 ]
Sun, Haopeng [1 ]
机构：
[1] China Pharmaceut Univ, Sch Pharm, Nanjing 211198, Jiangsu, Peoples R China
[2] Nanjing Univ Chinese Med, Sch Pharm, Nanjing 210023, Jiangsu, Peoples R China
[3] China Pharmaceut Univ, Dept Nat Med Chem, Nanjing 211198, Jiangsu, Peoples R China
来源：
CHINESE JOURNAL OF CHEMISTRY | 2022年 / 40卷 / 15期
基金：
中国国家自然科学基金;
关键词：
Alzheimer's disease; Butyrylcholinesterase; Inhibitors; Molecular modeling; Biological activity; TARGET-DIRECTED LIGANDS; BUTYRYLCHOLINESTERASE; ACETYLCHOLINESTERASE; ANTIOXIDANT; INHIBITION; ANALOGS; DESIGN; POTENT; MODEL;
D O I：
10.1002/cjoc.202200096
中图分类号：
O6 [化学];
学科分类号：
0703 ;
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 A beta(1-42) aggregation and A beta(1-42) induced SH-SY5Y cell injury. Altogether, these factors indicated their potential as unique lead compounds for AD treatment.
引用
收藏
页码：1821 / 1830
页数：10
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