Computational Simulation of Monoamine Oxidase (PDB ID: 2BXR) “Molecular Docking, Molecular Dynamics, and 3D-QSAR Analysis of 10H-Phenothiazin-1-yl Derivatives Targeting Enzymes”

Abstract

Background: This study focuses on the computational (in silico) analysis of 1H-phenothiazine derivatives to estimate their pharmacological potential, particularly as inhibitors of monoamine oxidase (PDB ID: 2BXR), an enzyme linked to depression. Using assorted computational methods, the study investigates structure-activity relationships and predicts the impact of structural changes on drug effectiveness. Results show that several compounds demonstrated significant cytotoxic activity against depression-related targets, suggesting promising inhibitory and anti-inflammatory properties. This work attempts to examine the inflammatory and enzyme-inhibitory properties of a novel series of 1H-phenothiazin derivatives in order to determine whether they may be used as multi-action therapeutic drugs. Combi Lab studies and 3D-QSAR were carried out using the Molecular Design Suite. Molecular docking analysis was conducted using Schrodinger Maestro. Out of the sixteen compounds made utilizing a Combinatorial technique, five compounds (PS6; PS5; PS11; PS13, and PS15) showed greater projected biological activity compared to the dataset’s most active molecule. The amino acid residues on monoamine oxidase (PDB ID: 2BXR) (PDB: 3LN1), including Val-349, Tyr-385, Phe-518, Trp-387, Gly-526, Tyr348, Met-522, Leu-352, Phe381, Leu-384, and Tyr-385 were in close proximity to these substances.

Keywords: ADMET; Depression; Molecular docking; COX-1 (PDB: 3KK6) and Monoamine oxidase; (PDB ID: 2BXR) (PDB: 3LN1); Phenothiazine