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Mini-Reviews in Medicinal Chemistry

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

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Review Article

A Recent Appraisal of Small-Organic Molecules as Anti-Alzheimer’s Agents

Author(s): Mohan Gupta, Avinash Kumar, Madhwi Ojha, Shabana Kausar Khan and Sumitra Nain*

Volume 23, Issue 8, 2023

Published on: 21 October, 2022

Page: [962 - 976] Pages: 15

DOI: 10.2174/1389557522666220922105934

Price: $65

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Abstract

Background: Alzheimer’s disease (AD) is an irreversible, progressive and very complex brain disorder. There is still uncertainty about the etiology of AD; however, a few hallmarks like an aggregation of tau proteins, amyloid-β plaques, oxidative stress, low level of choline in the brain etc., play significant roles.

Objective: In the present work, we aim to evaluate the recent progress in the development of small organic molecules containing heterocycles like thiazole, pyridines, dihydropyridines, piperidines, pyrrolidines, pyrazoles, quinolines etc. as anti-Alzheimer’s agents.

Methods: Several databases, including SciFinder, ScienceDirect, Bentham Science, and PubMed, were searched for relevant articles and reviewed for the present work.

Results: Several research groups are actively working on these heterocycle-based compounds as potent single-target inhibitors. Most of the analogues have been evaluated for their cholinesterase (acetylcholinesterase and butyrylcholinesterase) inhibition potential. Several studies have also reported the inhibitory potential of the analogues against MAO-A, MAO-B, and BACE-1 enzymes. However, instead of targeting one enzyme or protein, more than one heterocycle ring is being joined to develop MTDLs (multi-target-directed ligands). Donepezil has become the focal point of anti-AD drug discovery projects. Several research groups have reported various donepezil-based analogues by replacing/ modifying its various ring systems like indanone, piperidine or the methylene linker.

Conclusion: Small molecules with nitrogen-containing heterocycles have become the core of drug discovery efforts for AD. With the increasing prominence of the MTDL approach, several new ligands are being discovered as potent anti-AD agents.

Keywords: Acetylcholinesterase inhibitors, Brain disorders, Dementia, Donepezil, β-secretase inhibitors, Neurodegeneration

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