Design, synthesis and biological evaluation of novel indanones derivatives as potent acetylcholinesterase/monoamine oxidase B inhibitors

Hu, Zhaoxin; Zhou, Shengnan; Li, Junda; Li, Xinnan; Zhou, Yang; Zhu, Zheying; Xu, Jinyi; Liu, Jie

Abstract

Aim: Based on a multitarget design strategy, a series of novel indanone-1-benzyl-1,2,3,6-tetrahydropyridin hybrids were identified for the potential treatment of Alzheimer's disease (AD). Results: These compounds exhibited significant inhibitory activities against acetylcholinesterase (AChE) and moderate inhibitory activities toward monoamine oxidase B (MAO-B). The optimal compound A1 possessed excellent dual AChE/MAO-B inhibition both in terms of potency (AChE: IC50 = 0.054 ± 0.004 μM; MAO-B: IC50 = 3.25 ± 0.20 μM), moderate inhibitory effects on self-mediated amyloid-β (Aβ) aggregation and antioxidant activity. In addition, compound A1 exhibited low neurotoxicity. More importantly, compound A1 showed significant cognitive and spatial memory improvements in the scopolamine-induced AD mouse model. Conclusion: All results suggest that compound A1 may become a promising lead of anti-AD drug for further development.

Citation

Hu, Z., Zhou, S., Li, J., Li, X., Zhou, Y., Zhu, Z., …Liu, J. (2023). Design, synthesis and biological evaluation of novel indanones derivatives as potent acetylcholinesterase/monoamine oxidase B inhibitors. Future Medicinal Chemistry, 15(20), 1823-1841. https://doi.org/10.4155/fmc-2023-0206

• Journal Article Type: Article
• Acceptance Date: Sep 18, 2023
• Online Publication Date: Oct 30, 2023
• Publication Date: Oct 30, 2023
• Deposit Date: Nov 23, 2023
• Publicly Available Date: Jan 31, 2024
• Journal: Future Medicinal Chemistry
• Print ISSN: 1756-8919
• Electronic ISSN: 1756-8927
• Publisher: Future Science
• Peer Reviewed: Peer Reviewed
• Volume: 15
• Issue: 20
• Article Number: mc-2023-0206
• Pages: 1823-1841
• DOI: https://doi.org/10.4155/fmc-2023-0206
• Keywords: AChE; Alzheimer's disease; indan-1-one; MAO-B; MTDLs
• Public URL: https://nottingham-repository.worktribe.com/output/26811870
• Publisher URL: https://www.future-science.com/doi/full/10.4155/fmc-2023-0206