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

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

Volume: 21 Issue: 15

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

Affiliation:

• School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, 264005,China

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

Abstract: 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.

Cite this article as:

Tian Sen , Huang Zhongwei, Meng Qingguo and Liu Zongliang *, Multi-Target Drug Design of Anti-Alzheimer’s Disease based on Tacrine, Mini-Reviews in Medicinal Chemistry 2021; 21 (15) . https://dx.doi.org/10.2174/1389557521666210212151127