A comprehensive review of multi-target directed ligands in the treatment of Alzheimer’s disease

[Display omitted] Alzheimer’s disease (AD) is the most common form of dementia affecting specifically older population. AD is an irreversible neurodegenerative CNS disorder associated with complex pathophysiology. Presently, the USFDA has approved only four drugs viz. Donepezil, Rivastigmine, Memant...

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Bibliographic Details
Published in:Bioorganic chemistry 2024-03, Vol.144, p.107152-107152, Article 107152
Main Authors: Pathak, Chandni, Kabra, Uma D.
Format: Article
Language:English
Subjects:
Acetylcholinesterase
Alzheimer Disease - drug therapy
Alzheimer Disease - pathology
Alzheimer’s disease
Amyloid β aggregation
Butyrylcholinesterase
Cholinesterase inhibitors
Cholinesterase Inhibitors - pharmacology
Cholinesterase Inhibitors - therapeutic use
Dementia
Donepezil - therapeutic use
Humans
Ligands
Multi-target directed ligand
Oxidative stress
Rivastigmine - therapeutic use
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Summary:[Display omitted] Alzheimer’s disease (AD) is the most common form of dementia affecting specifically older population. AD is an irreversible neurodegenerative CNS disorder associated with complex pathophysiology. Presently, the USFDA has approved only four drugs viz. Donepezil, Rivastigmine, Memantine, and Galantamine for the treatment of AD. These drugs exhibit their neuroprotective effects either by inhibiting cholinesterase enzyme (ChE) or N-methyl-d-aspartate (NMDA) receptor. However, the conventional therapy “one target, one molecule” has failed to provide promising therapeutic effects due to the multifactorial nature of AD. This triggered the development of a novel strategy called Multi-Target Directed Ligand (MTDL) which involved designing one molecule that acts on multiple targets simultaneously. The present review discusses the detailed pathology involved in AD and the various MTDL design strategies bearing different heterocycles, in vitro and in vivo activities of the compounds, and their corresponding structure–activity relationships. This knowledge will allow us to identify and design more effective MTDLs for the treatment of AD.
ISSN:0045-2068
1090-2120
DOI:10.1016/j.bioorg.2024.107152