Xinnan Li
Novel and Potent Acetylcholinesterase Inhibitors for the Treatment of Alzheimer’s Disease from Natural (±)-7,8-Dihydroxy-3-methyl-isochroman-4-one
Li, Xinnan; Jia, Yilin; Li, Junda; Zhang, Pengfei; Li, Tiantian; Lu, Li; Yao, Hequan; Liu, Jie; Zhu, Zheying; Xu, Jinyi
Authors
Yilin Jia
Junda Li
Pengfei Zhang
Tiantian Li
Li Lu
Hequan Yao
Jie Liu
ZHEYING ZHU Zheying.Zhu@nottingham.ac.uk
Associate Professor in International Pharmacy and Traditional Medicines
Jinyi Xu
Abstract
Alzheimer’s disease (AD) is a neurodegenerative disease that causes memory and cognitive decline as well as behavioral problems. It is a progressive and well recognized complex disease; therefore, it is very urgent to develop novel and effective anti-AD drugs. In this study, a series of novel isochroman-4-one derivatives from natural (±)-7,8-dihydroxy-3-methyl-isochroman-4-one [(±)-XJP] were designed and synthesized, and their anti-AD potential was evaluated. Among them, compound 10a [(Z)-3-acetyl-1-benzyl-4-((6,7-dimethoxy-4-oxoisochroman-3-ylidene)methyl)pyri-din-1-ium bromide] possessed potent anti-acetylcholinesterase (AChE) activity as well as modest antioxidant activity. Further molecular modeling and kinetic investigations revealed that compound 10a was a dual-binding inhibitor that binds to both catalytic anionic site (CAS) and peripheral anionic site (PAS) of the enzyme AChE. In addition, compound 10a exhibited low cytotoxicity and moderate anti-Aβ aggregation efficacy. Moreover, the in silico screening suggested that these compounds could pass across the blood–brain barrier with high penetration. These findings show that compound 10a was a promising lead from a natural product with potent AChE inhibitory activity and deserves to be further developed for the prevention and treatment of AD.
Citation
Li, X., Jia, Y., Li, J., Zhang, P., Li, T., Lu, L., …Xu, J. (2022). Novel and Potent Acetylcholinesterase Inhibitors for the Treatment of Alzheimer’s Disease from Natural (±)-7,8-Dihydroxy-3-methyl-isochroman-4-one. Molecules, 27(10), Article 3090. https://doi.org/10.3390/molecules27103090
Journal Article Type | Article |
---|---|
Acceptance Date | May 9, 2022 |
Online Publication Date | May 11, 2022 |
Publication Date | May 11, 2022 |
Deposit Date | May 14, 2022 |
Publicly Available Date | May 17, 2022 |
Journal | Molecules |
Electronic ISSN | 1420-3049 |
Publisher | MDPI |
Peer Reviewed | Peer Reviewed |
Volume | 27 |
Issue | 10 |
Article Number | 3090 |
DOI | https://doi.org/10.3390/molecules27103090 |
Public URL | https://nottingham-repository.worktribe.com/output/8049796 |
Publisher URL | https://www.mdpi.com/1420-3049/27/10/3090 |
Files
Novel and Potent Acetylcholinesterase Inhibitors
(2.6 Mb)
PDF
Publisher Licence URL
https://creativecommons.org/licenses/by/4.0/
You might also like
The structural modification of natural products for novel drug discovery
(2016)
Journal Article
Downloadable Citations
About Repository@Nottingham
Administrator e-mail: discovery-access-systems@nottingham.ac.uk
This application uses the following open-source libraries:
SheetJS Community Edition
Apache License Version 2.0 (http://www.apache.org/licenses/)
PDF.js
Apache License Version 2.0 (http://www.apache.org/licenses/)
Font Awesome
SIL OFL 1.1 (http://scripts.sil.org/OFL)
MIT License (http://opensource.org/licenses/mit-license.html)
CC BY 3.0 ( http://creativecommons.org/licenses/by/3.0/)
Powered by Worktribe © 2024
Advanced Search