In silico screening of naturally derived dietary compounds as potential butyrylcholinesterase inhibitors for Alzheimer’s disease treatment
Md. Tarikul Islam, Md. Aktaruzzaman, Chandan Barai, Farhan Ishrak Rafi, ATM Hasibul Hasan, Tasfiah Tasnim, Parvej Sarder, Ghadeer M. Albadrani, Muath Q. Al‐Ghadi, Amany A. Sayed, Mohamed M. Abdel‐Daim, Humayra Afroz Dona, Kishore Kumar Sarkar, Md. Obayed Raihan
Abstract
Alzheimer's disease (AD) is a progressive neurodegenerative condition that causes a substantial decline in cognitive functions and affects memory, thinking abilities, and daily behavior. The most prominent hallmark of AD pathogenesis is the formation of amyloid-β plaques, among other associated pathways such as neurofibrillary tangles, mitochondrial dysfunction, neuroinflammation, and oxidative stress. Butyrylcholinesterase (BuChE), an acetylcholine-degrading enzyme, plays a critical role in the progression of Alzheimer's disease, particularly through its involvement in amyloid-β plaque formation. Thus, the inhibition of BuChE is considered a valuable therapeutic strategy for the management of AD. The present study aimed to identify potential bioactive chemicals from naturally occurring dietary compounds that could improve neurocognitive function and appear as a viable treatment for AD by inhibiting the function of BuChE. A small library of 44 natural dietary chemicals from a variety of dietary plants was subjected to comprehensive in silico studies, including molecular docking, molecular mechanics generalized born surface area (MM-GBSA) calculations, pharmacokinetics assessments, toxicity profiles, molecular dynamics (MD) simulation, and density functional theory (DFT) analysis. These studies revealed that CID 129886986 and CID 115269 showed stronger binding affinities with drug-likeness and no toxicity than the FDA-approved standard drug, Donepezil. Additionally, they exhibited strong structural stability with fewer fluctuations throughout the simulation, making them promising candidates for Alzheimer's disease treatment.