Latest advances in dual inhibitors of acetylcholinesterase and monoamine oxidase B against Alzheimer’s disease

Abstract

Alzheimer’s disease (AD) is a progressive brain disease characterised by progressive memory loss and cognition impairment, ultimately leading to death. There are three FDA-approved acetylcholinesterase inhibitors (donepezil, rivastigmine, and galantamine, AChEIs) for the symptomatic treatment of AD. Monoamine oxidase B (MAO-B) has been considered to contribute to pathologies of AD. Therefore, we reviewed the dual inhibitors of acetylcholinesterase (AChE) and MAO-B developed in the last five years. In this review, these dual-target inhibitors were classified into six groups according to the basic parent structure, including chalcone, coumarin, chromone, benzo-fused five-membered ring, imine and hydrazine, and other scaffolds. Their design strategies, structure-activity relationships (SARs), and molecular docking studies with AChE and MAO-B were analysed and discussed, giving valuable insights for the subsequent development of AChE and MAO-B dual inhibitors. Challenges in the development of balanced and potent AChE and MAO-B dual inhibitors were noted, and corresponding solutions were provided.

Keywords:

• Alzheimer’s disease
• AChE inhibitors
• MAO-B inhibitors
• dual inhibitors

Authors contributions

Writing-original draft preparation, Dajiang Zou; writing-review and editing, Dajiang Zou, Renzheng Liu, Yangjing Lv, Jianan Guo, Changjun Zhang; supervision, Yuanyuan Xie. All authors have read and agreed to the published version of the manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This project was supported by the Zhejiang Key R&D Program (No. 2021C03085); National Key R&D Program of China (2021YFC2100800); National Natural Science Foundation of China, NSFC (Grant No. 21978273 and 22378360); China Postdoctoral Science Foundation, CPSF (No. 2021M702897).