In-silico screening and ADMET evaluation of therapeutic MAO-B inhibitors against Parkinson disease

Abstract

MAOs are flavoenzymes that aid in the oxidative deamination of neurotransmitters such as dopamine, serotonin, and epinephrine. MAO inhibitors are antidepressants that act by inhibiting neurotransmitter breakdown in the brain and controlling mood. MAO inhibitors with the chlorophenyl-chromone-carboxamide structure have been shown in investigations to be extremely effective. The current study employs in-silico screening, MD simulation, and drug kinetics evaluation, all of which are evaluated using different criteria. The study comprised 37 ligands, and three stood out as the best, with greater binding scores above the threshold value. Docking analysis found that compound 34 had the highest docking score in the series (−13.60 ​kcal/mol) and interacted with the important amino acids TYR 435, CYS 397, CYS 172, PHE 343, TYR 398, and LYS 296 required for MAO inhibitory activity. The ADMET study revealed that the compounds had drug-like properties. The results of this study could be used to develop chromone drugs that target the MAO inhibitor. The top three ligands with the highest force and work were then simulated using molecular dynamics. The protein-ligand complexes had steady trajectories throughout the 100 ns simulation, according to the data. Furthermore, the drug likeliness predicted by ADMET analysis findings indicated that the top three lead compounds had strong inhibitory efficiency, superior pharmacokinetics, and were non-toxic under physiological settings. As a result, these compounds have the potential to be exploited as possible treatment medications for PD.