Identification of Natural Compounds of the Apple as Inhibitors against Cholinesterase for the Treatment of Alzheimer's Disease: An In Silico Molecular Docking Simulation and ADMET Study

Alzheimer's disease (AD), the most common type of dementia in older people, causes neurological problems associated with memory and thinking. The key enzymes involved in Alzheimer's disease pathways are acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Because of this, there is a lot of interest in finding new AChE inhibitors. Among compounds that are not alkaloids, flavonoids have stood out as good candidates. The apple fruit, Malus domestica (Rosaceae), is second only to cranberries regarding total phenolic compound concentration. Computational tools and biological databases were used to investigate enzymes and natural compounds. Molecular docking techniques were used to analyze the interactions of natural compounds of the apple with enzymes involved in the central nervous system (CNS), acetylcholinesterase, and butyrylcholinesterase, followed by binding affinity calculations using the AutoDock tool. The molecular docking results revealed that CID: 107905 exhibited the best interactions with AChE, with a binding affinity of -12.2 kcal/mol, and CID: 163103561 showed the highest binding affinity with BuChE, i.e., -11.2 kcal/mol. Importantly, it was observed that amino acid residue Trp286 of AChE was involved in hydrogen bond formation, Van Der Walls interactions, and Pi-Sigma/Pi-Pi interactions in the studied complexes. Moreover, the results of the Molecular Dynamics Simulation (MDS) analysis indicated interaction stability. This study shows that CID: 12000657 could be used as an AChE inhibitor and CID: 135398658 as a BuChE inhibitor to treat Alzheimer's disease and other neurological disorders.