Chemical and Pharmaceutical Bulletin
Online ISSN : 1347-5223
Print ISSN : 0009-2363
ISSN-L : 0009-2363

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Discovery and biological evaluation of new selective acetylcholinesterase inhibitors with anti-Aβ aggregation activity through molecular docking-based virtual screening
Guangpu LiuYang JiaoYongqiang LinHaifang HaoYanli DouJuan YangCheng-Shi JiangPing Chang
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JOURNAL FREE ACCESS Advance online publication

Article ID: c19-00927

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Abstract

Discovery of novel multifunctional inhibitors targeting 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 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-Aβ aggregation and neuroprotective activity were also well investigated. Our findings highlighted the therapeutic promise of AChE inhibitors A01-A04 for AD treatment.

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© 2019 The Pharmaceutical Society of Japan
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