Molecular dynamics simulation and structural characterization of (-)-carvone and cis-dihydrocarvone from Mentha piperita L. as potential MMP9 inhibitors for idiopathic pulmonary fibrosis therapy.

Authors

G Koteswara Reddy, Yuvaraj Dinakarkumar, Korukonda Satwik, Allam Sai Sree Thanay, Bobba Devi Sri Siddhartha, Nandigum Sai Anvesh, Selvaraj Arokiyaraj, Panneerselvam Theivendren

Published in

3 Biotech. Volume 16. Issue 1. Pages 9. Epub Dec 08, 2025.

Abstract

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease involving dysregulated matrix metalloproteinase-9 (MMP9) activity, leading to excessive extracellular matrix deposition and lung tissue deterioration. This study investigated bioactive compounds from Mentha piperita L. as potential MMP9 inhibitors for IPF therapy. Gas chromatography-mass spectrometry (GC-MS) analysis identified nine phytochemicals in the methanolic extract of peppermint leaves. Drug-likeness screening using Lipinski's Rule of Five identified two lead compounds: (-)-carvone and cis-dihydrocarvone. ADMET analysis revealed favorable pharmacokinetic properties, including appropriate solubility (-3.089 and -3.12, respectively) and blood-brain barrier permeability values (0.345 and 0.357). TOPKAT toxicity prediction classified both compounds as non-carcinogenic with negligible skin sensitization potential. Molecular docking against MMP9 (PDB ID: 1GKD) yielded MolDock scores of -84.22 for (-)-carvone and  -87.47 for cis-dihydrocarvone, indicating strong binding affinity. Molecular dynamics simulations over 100 ns demonstrated stable protein-ligand complexes with consistent RMSD values (~ 0.8 Å for ligand), sustained hydrogen bonding interactions, and minimal conformational changes. Key residues LEU188, VAL398, HIS401, and TYR423 were identified as critical for binding stability. These computational findings establish (-)-carvone and cis-dihydrocarvone as promising MMP9 inhibitor candidates for IPF treatment, warranting in vitro and in vivo experimental validation.

PMID:
41376892
Bibliographic data and abstract were imported from PubMed on 11 Dec 2025.

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