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

作者：Xin Lü, Yijun Liu, Nan Qin, Chenxi Du, Yanyu Hu, Yao Chen, Haopeng Sun · 发表于：Chinese Journal of Chemistry · 年份：2022 · DOI：10.1002/cjoc.202200096 · 被引用次数：7 · 研究领域：Cholinesterase and Neurodegenerative Diseases、Computational Drug Discovery Methods、Medicinal Plants and Neuroprotection

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 Aβ 1‐42 aggregation and Aβ 1‐42 induced SH‐SY5Y cell injury. Altogether, these factors indicated their potential as unique lead compounds for AD treatment.