Selected phytochemicals as potent acetylcholinesterase inhibitors: An in silico prediction

In recent times, there has been a notable increase in the widespread presence of Alzheimer’s disease. The disease could be controlled by the inhibition of acetylcholinesterase, an enzyme associated with the degradation of acetylcholine. Plants have been used to treat neurogenerative diseases and the...

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Main Authors: Shrestha Ram Lal Swagat, Neupane Prabhat, Dhital Sujan, Parajuli Nirmal, Maharjan Binita, Shrestha Timila, Bharati Samjhana, Marasini Bishnu Prasad, Adhikari Subin Jhashanath
Format: Article
Language:English
Published: Serbian Chemical Society 2025-01-01
Series:Journal of the Serbian Chemical Society
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Online Access:https://doiserbia.nb.rs/img/doi/0352-5139/2025/0352-51392400065S.pdf
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Summary:In recent times, there has been a notable increase in the widespread presence of Alzheimer’s disease. The disease could be controlled by the inhibition of acetylcholinesterase, an enzyme associated with the degradation of acetylcholine. Plants have been used to treat neurogenerative diseases and their phytochemicals could act as acetylcholinesterase inhibitors, impeding the protein’s catalytic activity. This study includes a computational assessment of phytocompounds as potent inhibitors of the enzyme. The molecular docking calculations revealed binding affinities of −50.651, –49.446 , –48.400, –47.977, –47.839 and –47.417 kJ/mol for allanxanthone B, stigmasterol, 5'-O-methyl dioncophylline D, ismailin, wistin and dioncophylline C2, respectively, indicating firm binding of these molecules with the receptor. Donepezil (a native and FDA-approved drug) exhibited a binding affinity of –46.789 kJ/mol, which was significantly lower than that of the proposed phytochemicals. The successful candidates demonstrated good stability of the complex with the protein, showing smooth RMSD of ligands below 6 Å from the 200 ns molecular dynamics simulation. The thermodynamic stability from the MMPBSA method indicated the sustained spontaneity and feasibility of the adducts. Thus, the proposed candidates could be used as remedies for Alzheimer’s disease after the experimental verification for their safety and efficacy.
ISSN:0352-5139
1820-7421