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

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.