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., Xu, J., & 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