Molecular Docking Stufy Of Secondary Metabolites From Turmeric (Curcuma longa) As Potential MAO-A Inhibitors For Antistress Therapy

Abstract

Monoamine Oxidase A (MAO-A) is a key enzyme in neurotransmitter metabolism, making its inhibition a strategic approach for antistress  drug development. Turmeric (Curcuma longa) secondary metabolites possess potential therapeutic properties as MAO-A inhibitors. This study aims to evaluate the potential of turmeric secondary metabolites as MAO-A inhibitors through in silico molecular docking, pharmacokinetic profiling (ADME-Tox), drug-likeness evaluation, and subsequent structural modification of the lead compound. A computational approach was employed using 70 secondary metabolites from Curcuma longa L. Molecular docking was performed via PyRx-AutoDock Vina, followed by ADME-Tox and drug-likeness evaluation using SwissADME, pkCSM, and Toxtree, while structural modification was designed using ChemDraw. Demethylcurcumin emerged as the best candidate among seven top compounds, demonstrating a favorable binding affinity of -9.3 kcal/mol and an RMSD of 1.001 Å. Structural modification yielded a derivative, (4E,6E)-1-(3,4-dihydroxyphenyl)-7-hydroxyocta-4,6-dien-1-one, which exhibited improved drug-likeness, pharmacokinetic profiles, and toxicity parameters compared to the parent compound. Demethylcurcumin shows strong potential as a natural MAO-A inhibitor, and its structural derivative provides an enhanced pharmacological and safety profile for further antistress  drug development.