Identification of Potential Acetylcholinesterase (AChE) inhibitors from Vitis vinifera: A Case study of Alzheimer’s Disease (AD)

Abstract

Abstract Alzheimer’s disease (AD) is the most prevalent neurodegenerative disease that affects people aged 60 years and above. Yet, the discovery of potent therapeutic agents against this disease has no utmost progress and a number of drug candidates could not make it out of the clinical trials at varied stages. At the same time, the currently available anti-cholinesterase for the treatment of AD can only improve the clinical symptoms while the recently approved immunotherapy agent “remains questionable. Thus, the need for novel therapeutic agents with the potential to treat the aetiology of the disease. Herein, this study sought to examine the potential of a number of bioactive compounds derived from Vitis vinifera as a promising agent against AChE. Using a computational approach via molecular docking 23 bioactive agents were screened against AChE and the compounds with a binding score below that of the standard ligand were further subjected to drug-likeness and pharmacokinetic screening. Eight of the studied agents optimally saturated the active pocket of the AChE, forming principal interactions with a number of amino acids at its active pocket and among these compounds only rutin failed the drug-likeness test by violating four parameters while all showed moderate pharmacokinetics features. A number of Vitis vinifera-derived bioactive compounds show excellent inhibitory potential against AChE and moderate pharmacokinetic features when compared to the reference ligand (tacrine). These compounds are therefore proposed as novel AChE inhibitors for the treatment of AD and wet-lab analysis is necessary to affirm their potency.