QSAR, Molecular Docking, Dynamic Simulation and Kinetic Study of Monoamine Oxidase B Inhibitors as Anti-Alzheimer Agent

Alzheimer's disease (AD) is a neurological ailment that affects the elderly, causes dementia and cognitive impairment. The disease's specific mechanism has yet to be uncovered. New drugs that are effective against this ailment are being search for by the medical scientist community. Here, Chemometrics and in-silico techniques were employed. MAO-B inhibitors provide exciting therapeutic potential to treat AD in its many forms. A QSAR model with the following properties were generated; ALogP (31%), ATS3v (27%), BCUTc-1l (21%), and TIC0 (21%). Also, the protein target formed very good interactions with the inhibitors and interacted majorly with hydrogen bonding, and docking scores of - 44.1 kcal/mol (compound 41), - 50.1 kcal/mol (compound 42), and - 41.8 kcal/mol (compound 43) and - 14.7 kcal/mol for the referenced compound. Furthermore, Molecular dynamics simulation of 100 ns was carried out to verify the docking analysis using the compound with highest docking score which is compound 42 (docked complex), during the simulation, the results confirmed the stiffness of the protein-ligand complex. Predicted physicochemical computed data revealed that none of the inhibitors violated Lipinski's Ro5, implying orally bioavailable as possible therapeutic candidates. The in-silico results showed thoroughly gastrointestinally absorbed, and have a low ADMET risk of permeating into the brain, hence it can be utilized as a novel therapeutic candidates.