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Mini-Reviews in Medicinal Chemistry


ISSN (Print): 1389-5575
ISSN (Online): 1875-5607

Mini-Review Article

Multi-Target Drug Design of Anti-Alzheimer’s Disease based on Tacrine

Author(s): Sen Tian, Zhongwei Huang, Qingguo Meng and Zongliang Liu*

Volume 21, Issue 15, 2021

Published on: 12 February, 2021

Page: [2039 - 2064] Pages: 26

DOI: 10.2174/1389557521666210212151127

Price: $65


Alzheimer's disease (AD) is a progressive neurodegenerative disease with concealed onset, which is characterized by the damage of the cholinergic system, deposition, and accumulation of β- amyloid protein (Aβ) and neurofibrillary tangles. Because the cholinergic system plays a key role in the process of brain memory, it has become one of the important targets in anti-AD research. In view of the complicated pathological characteristics of AD, the multi-target directed ligands (MTDLs) that can act on multiple targets are considered to be an effective treatment strategy at present. Tacrine, as the first acetylcholinesterase (AChE) inhibitor, has been discontinued because of its hepatotoxicity, but its core structure is simple and easy to modify. By using tacrine to target the active catalytic site (CAS), the tacrine-based MTDLs can act on both CAS and peripheral anion site (PAS) of AChE to serve as a dual-site AChE inhibitor. Additionally, the tacrine-based MTDLs can also be designed on the basis of other theories of AD, for example, introducing functional moieties to modulate the formation of β-amyloid (Aβ), oxidation resistance, or metal chelation. In this paper, the research progress of tacrine-based MTDLs is summarized.

Keywords: Alzheimer's disease, acetylcholinesterase, tacrine, structural transformation, multi-target-directed ligands, multifunctional molecules.

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