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

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.

Materials and Methds

Using assorted computational methods, the study investigates structure-activity relationships and predicts the impact of structural changes on drug effectiveness.

Results

Results show that several compounds demonstrated significant cytotoxic activity against depression-related targets, suggesting promising inhibitory and anti-inflammatory properties. The aim of this work was 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.

Conclusion

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 Tyr-385, Trp-387, Phe-518, Gly-526, Met-522, Tyr348, Val-349, Leu-352, Phe381, Leu-384, and Tyr-385were in close proximity to these substances.