Selected phytochemicals as potent acetylcholinesterase inhibitors: An in silico prediction Scientific paper

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Ram Lal Swagat Shrestha
https://orcid.org/0000-0002-7939-2830
Prabhat Neupane
https://orcid.org/0009-0001-8256-7072
Sujan Dhital
https://orcid.org/0009-0000-2384-1687
Nirmal Parajuli
https://orcid.org/0009-0008-7068-6374
Binita Maharjan
https://orcid.org/0009-0002-5606-3257
Timila Shrestha
https://orcid.org/0009-0008-2686-6378
Samjhana Bharati
https://orcid.org/0009-0002-4301-7251
Bishnu Prasad Marasini
https://orcid.org/0000-0001-6153-5234
Jhashanath Adhikari Subin
https://orcid.org/0000-0001-8515-9843

Abstract

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.

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How to Cite
[1]
R. L. S. Shrestha, “Selected phytochemicals as potent acetylcholinesterase inhibitors: An in silico prediction: Scientific paper”, J. Serb. Chem. Soc., vol. 90, no. 2, pp. 187–200, Feb. 2025.
Section
Theoretical Chemistry

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