Exploring Chroman‐4‐One Derivatives as MAO‐B Inhibitors: A Comprehensive Computational Study

Abstract

The enzyme monoamine oxidase‐B (MAO‐B) significantly affects the neurotransmitter's metabolism, including norepinephrine, dopamine, and serotonin. Alzheimer's disease is the result of the dysregulation of MAO‐B activity, which is also attached to another neurological disorder, that is, Parkinson's disease. The MAO‐B antagonists are now seen as potential therapeutics for these conditions. A promising approach for improving the effectiveness of novel MAO inhibitors is using chromanone scaffolds. In this work, we used a multimodal computational approach to assess the inhibitory effects of chroman‐4‐one derivatives on MAO‐B. The study utilized molecular docking methodologies to investigate and evaluate the intricate binding interactions between MAO‐B and chroman‐4‐one derivatives. Moreover, the ADME study provided insightful information about the pharmacokinetic characteristics of chroman‐4‐one derivatives. The analysis of the temporal stability and dynamic behavior of ligand‐protein interactions has benefited from the application of MD simulations. To determine the binding free energies and gain a deeper comprehension of the binding affinity between chroman‐4‐one derivatives and MAO‐B, MM‐PBSA calculations were also performed. This study offers valuable information about logical design and the optimization of MAO‐B antagonists and highlights the potential of computational techniques in speeding up the drug discovery process.