Alzheimer's Disease (AD) is one of the most common forms of dementia in elderly people.
To date, efficacious therapeutic agent for the treatment of AD is still very limited, so it has long
been a challenging and attractive task to discover new anti-AD drugs. Considering the multifactorial
nature of AD, recently, the concept of Multi-Target-Directed Ligands (MTDLs) has emerged as a
new strategy for designing therapeutic agents on AD. MTDLs are believed to exert their effects
through simultaneously affecting multiple targets which contribute to etiology of AD. Therefore,
MTDLs are considered to be more efficacious than mono-target agents. Tacrine is the first drug approved
by Food and Drug Administration (FDA). Although the clinical use of tacrine is restricted because
of its hepatotoxicity, the high Ligand Efficiency (LE) of this compound makes it an ideal component
for designing MTDLs. This article provides an update review of the advances on the development
of MTDLs based on tacrine. Case studies are carefully selected to show the detailed strategy
on medicinal modification of Tacrine-Based MTDLs. Finally, several concerns and opinions on designing
new MTDLs are discussed as well.
Keywords: Alzheimer`s Disease, Multi-target-directed ligands (MTDLs), Tacrine, Hybrids, Acetylcholinesterase inhibitors,
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