Selected phytochemicals as potent acetylcholinesterase inhibitors: An in silico prediction

Abstract

In recent times, there has been a notable increase in the prevalence of Alzheimer?s disease. The disease could be managed through 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 kJ/mol, -49.446 kJ/mol, - 48.400 kJ/mol, -47.977 kJ/mol, -47.839 kJ/mol, 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 hit candidates demonstrated good stability of the complex with the protein, showing smooth RMSD of ligands below 6 ? 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 hit candidates could be used as remedies for Alzheimer?s disease after experimental verification for their safety and efficacy.