A Comparative Study of Binding Interactions of Natural Flavonoids and Conventional Drug Donepezil for Multiple Alzheimer's Disease Targets Using In silico Approach

Abstract

Background: Alzheimer's disease (AD) is one of the major causes of morbidity, affecting more than 36 million population worldwide. Current anti-AD treatments result in limited therapeutic outcomes owing to the complexity of the disease. Some natural promising herbal drugs and phytoconstituents utilized as an alternative treatment for AD have been reported by several researchers for their neuroprotective action. Objective: This study aimed at carrying out molecular docking studies of selected promising flavonoids such as curcumin, quercetin, bilobalide, ferulic acid, reseveratrol for their molecular interactions with multiple AD target proteins and further compare the data with the standard acetylcholine esterase inhibitor drug donepezil. Methods: The molecular docking interactions were studied between the selected actives and the AD target proteins acetylcholine esterase, butyrylcholine esterase, and tau protein using the AutoDock Vina software. The Swiss ADME approach performed prediction of the ADME properties. Binding interactions of the ligands at the target protein binding sites were examined using the Discovery Studio Visualizer 2021. Results: The binding energy for quercetin in the active site of the selected target enzymes acetylcholine esterase, butyrylcholine esterase, and tau protein was -9.5 , -7.8 , and -8.2 kcal/mol, respectively which was much greater than other flavonoids and comparable to the standard drug donepezil binding energy - 10.3, -7.5,-7.9 kcal/mol respectively. Conclusion: This work focuses on recognizing structural features and comparing selected flavonoids and standard acetylcholine esterase (AChEs) inhibitors for molecular docking with three primary targets of AD, namely AChEs, Butyrylcholine esterase, and tau protein. This in silico study concluded that quercetin had significant docking interactions and good pharmacokinetic features, making it a potential therapeutic candidate for the treatment of AD.