Design of New Inhibitory Ligands of Monoamine Oxidase A-Enzyme for Use in the Control of Depression and Mental Disorders Using Bioinformatics Tools

Monoamine oxidase A-enzyme (MAO-A) and MAO-B inhibitors are involved in the treatment of some diseases of the nervous system and regulate the expression of cytokine genes associated with inflammation and various diseases.

After selecting the inhibitory reference compound of MAO-A with the help of bioinformatic tools, such as ZINC15 and ZINCPHARMER, for virtual search through the structural and pharmacophoric properties of the reference inhibitory compound, several new ligands were obtained. Then, compariosn between the ligands with MAO-A docking process was performed and the selected top ligands in terms of toxicity, allergy, toxicity, and ADME prediction with tools, such as molsoft, PKCSM, way2drug swiss MADE, were examined.

Among the top four final ligands obtained, LIG52 had the highest interaction with different residues and with higher docking binding energy (vina score = -9.7) than the others, followed by IG48 and LIG54. Among the effective interacting residues, Trp128, ASN125, and GLU492 were bound to MAO-A in superior ligands, such as the reference compound. They also had the desired ability to interact with residues involved in substrate selectivity and catalytic activity, inhibition, and disruption of MAO-A activity.

The ligands obtained in this study were able to have different interactions with the appropriate number of rotatable bonds on physicochemical properties and spatial orientation at the site of binding to MAO-A. Furthermore, the results obtained from different servers that investigated the molecular properties and drug similarity of toxicity and absorption of metabolism, secretion, and release of inhibitory ligand compounds were obtained. Therefore, they can be considered as possible drug compounds in biological systems after further studies in laboratory and clinical conditions.