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2000
Volume 32, Issue 21
  • ISSN: 0929-8673
  • E-ISSN: 1875-533X
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Abstract

Introduction

Alzheimer’s Disease (AD) is a complicated and advanced neurodegenerative condition accompanied by gradual cholinergic neuronal death and higher levels of monoamine oxidase-B (MAO-B) enzyme. In this study, a series of novel hybrid compounds combining 1,3,4-oxadiazole and quinoline moieties were synthesized and evaluated for their potential as inhibitors of acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), and MAO enzymes.

Methods

The chemical structures of the synthesized compounds were confirmed using various analytical techniques, such as mass spectrometry, infrared spectroscopy (IR), proton nuclear magnetic resonance (1H-NMR), and carbon and nuclear magnetic resonance (13C-NMR). The final products were evaluated for anticholinesterase potential by applying modified Ellman’s spectrometric method, whereas a fluorometric method was used to assess MAO inhibition properties. studies using molecular docking and molecular dynamics simulation (MDS) methods has been also conducted.

Results

Among the synthesized compounds, 5a, 5c, and 6a demonstrated substantial activity against AChE, with IC values of 0.033 µM, 0.096 µM, and 0.177 µM, respectively. A molecular docking study was performed to elucidate the binding modes and establish the structure-activity relationship (SAR) of the most active compounds (5a, 5c, and 6a). Molecular dynamics simulation (MDS) of the most potent compound, 5a, was also conducted to examine the stability of the interactions with the receptor. Moreover, the physicochemical properties of the active products were also studied.

Conclusion

Overall, this research contributes to the development of 1,3,4-oxadiazole-quinoline hybrids as potential AChE inhibitors for the treatment of Alzheimer’s disease.

© 2025 The Author(s).
Published by Bentham Science Publisher. This is an open access article published under CC BY 4.0 https://creativecommons.org/licenses/by/4.0/legalcode
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Exploring Novel Quinoline-1,3,4-Oxadiazole Derivatives for Alzheimer’s Disease: Their Design, Synthesis, and In-Vitro and In-Silico Investigations
Curr. Med. Chem. 32, 4259 (2025); https://doi.org/10.2174/0109298673333159240815061359
/content/journals/cmc/10.2174/0109298673333159240815061359
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  • Article Type:     Research Article
Keyword(s): 1,3,4-oxadiazole; Alzheimer’s disease; anticholinesterase; molecular docking; quinoline; β-amyloid plaques

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