In Silico Molecular Docking Analysis of Natural Compounds as Potential BACE1 Inhibitors in Alzheimer’s Disease

Abstract

Alzheimer's Disease is a neurodegenerative disease in the elderly, it involves progressive loss of memory, cognition, and behavior changes. Amyloid-beta plaques that arise from the activity of Beta-site Amyloid Precursor Protein Cleaving Enzyme 1 (BACE1) are a dominant pathological hallmark. In the present work, Molecular docking study of several natural alkaloids was carried out to screen its potency to be an inhibitor of BACE1 enzyme with the application of computational drug design approaches. The tested compounds were berberine, physostigmine, galantamine, reserpine, harmine, piperine, corycavamine, palmatine, jatrorrhizine, corynoline, and mahanimbine. We then compared the docking result with the known synthetic drug for anti-Alzheimer, rivastigmine. Molecular docking was carried out with AutoDock Vina, and interaction with active site of BACE1 was evaluated with visualizer tool. The selected natural alkaloids showed good binding affinity to the active site of BACE1 enzyme. Amongst all the compounds studied, the result demonstrated that reserpine, mahanimbine, berberine, and corycavamine show better docking values and lower binding energy than rivastigmine. The interactions that formed were primarily through hydrogen bond, hydrophobic interaction and aromatic stacking with active site residues. The present study indicates that some of the natural alkaloids can be proposed as potential lead molecules in designing new anti-Alzheimer agents. Also, it emphasizes on the significance of Molecular Docking as an efficient and economical approach in modern drug discovery process for the development of anti-Alzheimer's drug.