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 major cause of morbidity in world, affecting about 5.8 million and 4 million people in India. Current anti-AD treatments are limited in their usage. Objective: Some natural promising herbal drugs that might be utilised as an alternative treatment for AD have been reported by several researchers for their neuroprotective action. Based on this, we chose these flavonoids Curcumin, Quercetin, Bilobalide, Ferulic acid, Reservetrol and donepezil (conventional Acetylcholine esterase inhibitor) as ligands for molecular docking studies. Methods: The Molecular docking interactions studied between these components with Acetylcholine esterase, Butyrylcholine esterase, and tau protein by Auto dock software. Prediction of ADME properties were performed by Swiss ADME. Binding interactions of the ligands at target protein binding sites were examined using Discovery studio visualizer 2021. Results: The binding energy for quercetin in the active site of enzymes was -9.5 , -7.8 , -8.2 kcal/mol which was much greater than other flavonoids and comparable to standard drug donepezil binding energy -10.3, -7.5,-7.9 kcal/mol. Quercetin in combination with standard AChEs inhibitor, could be alternative treatment for AD. Conclusion: This work focuses on recognizing structural features and comparing selected flavonoids and conventional Acetylcholine esterase (AChEs) inhibitor 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 potentially therapeutic candidates for the treatment of AD indicating future studies will be needed.