标题：Discovery and Biological Evaluation of New Selective Acetylcholinesterase Inhibitors with Anti-Aβ Aggregation Activity through Molecular Docking-Based Virtual Screening
作者：Liu G.; Jiao Y.; Lin Y.; Hao H.; Dou Y.; Yang J.; Jiang C.-S.; Chang P.
作者机构：[Liu, G] Department of Pharmacy, Qilu Hospital of Shandong University;[ Jiao, Y] Shandong Institute for Food and Drug Control;[ Lin, Y] Shandong Insti 更多
来源：Chemical & pharmaceutical bulletin
关键词：amyloid beta aggregation; molecular docking; molecular dynamics simulation; neuroprotectant; selective acetylcholinesterase inhibitor
摘要：Discovery of novel multifunctional inhibitors targeting acetylcholinesterase (AChE) has becoming a hot spot in anti-Alzheimer's disease (AD) drug development. In the present study, four potent small molecule inhibitors (A01, A02, A03 and A04) of AChE with new chemical scaffold were identified. Inhibitor A03 displayed the most potent inhibition activity on AChE at enzymatic level with IC50 value of 180 nM, and high selectivity towards AChE over butyrylcholinesterase (BChE) by more than 100-fold. The binding modes of compounds A01-A04 were carefully analyzed by molecular docking and molecular dynamics (MD) simulation to provide informative clues for further structure modification. Finally, the anti-amyloid beta (Aβ) aggregation and neuroprotective activity were also well investigated. Our findings highlighted the therapeutic promise of AChE inhibitors A01-A04 for AD treatment.