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Current Drug Targets

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ISSN (Print): 1389-4501
ISSN (Online): 1873-5592

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Review Article

A Review on Recent Development of Novel Heterocycles as Acetylcholinesterase Inhibitor for the Treatment of Alzheimer’s Disease

Author(s): Ashish Patel*, Drashti Shah, Yug Patel, Stuti Patel, Meshwa Mehta and Tushar Bambharoliya

Volume 24, Issue 3, 2023

Published on: 03 February, 2023

Page: [225 - 246] Pages: 22

DOI: 10.2174/1389450124666221213114500

Price: $65

Abstract

Alzheimer's Disease (AD), affecting a large population worldwide, is characterized by the old population's loss of memory and learning ability. Cholinergic deficiency is associated with AD, and various cholinesterase inhibitors have been developed to treat AD, including naturallyderived inhibitors, synthetic analogs, and hybrids. Acetylcholinesterase (AChE) has obtained a renewed interest as a therapeutic target in Alzheimer's disease (AD) due to increased neural cells' function by increasing the concentration of acetylcholine. In this review, we reported the recent development of novel heterocyclic compounds such as coumarin-benzotriazole hybrids, carbazole derivatives, tacrine conjugates, N-benzyl-piperidine-aryl-acyl hydrazones hybrid, spiropyrazoline derivatives, coumarin-dithiocarbamate hybrids, etc., as AChE inhibitors for the treatment of Alzheimer disease. All the bioactive compounds show an effect on different cells and interact simultaneously with the catalytic active site (CAS) and peripheral anionic site (PAS) of AChE with a narrow range of IC50 values from 0.4 nm to 88.21 μm using Ellman’s in vitro AChE assay method and show high BBB permeability in vitro. In addition, the in vitro fluorescence assay study using Amplex Red assay kits revealed that all the compounds could inhibit self-induced β-amyloid (Aβ) aggregation with the highest inhibition range from 31.4 to 82%. Furthermore, most of the compounds show a low toxicity profile during in vivo studies. The results suggest that all the compounds constitute promising leads for the AChE targeted approach for Alzheimer’s disease.

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