Colchicine as potential inhibitor targeting MMP-9, NOX2 and TGF-β1 in myocardial infarction: a combination of docking...

Area of Science:

• Cardiovascular Research
• Molecular Biology
• Computational Chemistry

Background:

• Myocardial infarction (MI) is a leading cause of mortality globally, often leading to heart failure via cardiac remodeling.
• Matrix metalloproteinase-9 (MMP-9), NADPH oxidase 2 (NOX2), and transforming growth factor-beta 1 (TGF-β1) are key biomarkers influencing post-MI cardiac remodeling.
• Colchicine is increasingly used for cardiovascular diseases, but its molecular interactions in post-MI remodeling are not fully understood.

Purpose of the Study:

• To investigate the molecular interactions of colchicine with MMP-9, NOX2, and TGF-β1 using molecular docking and dynamics simulations.
• To assess colchicine's potential inhibitory effects on these key remodeling biomarkers.

Main Methods:

• Molecular docking simulations were performed to evaluate the binding affinity of colchicine with MMP-9, NOX2, and TGF-β1.
• Molecular dynamics simulations, including Root Mean Square Deviation (RMSD), Root Mean Square Fluctuation (RMSF), Solvent Accessible Surface Area (SASA), and Principal Component Analysis (PCA), were used to analyze interaction stability.
• Identification of key catalytic residues involved in colchicine binding.

Main Results:

• Colchicine exhibited strong binding affinities with MMP-9 (-8.3 Kcal/mol), NOX2 (-6.7 Kcal/mol), and TGF-β1 (-6.5 Kcal/mol).
• Colchicine interacted with critical catalytic residues in all three targets, suggesting inhibitory potential.
• Molecular dynamics simulations indicated stable interactions, particularly with MMP-9, supporting colchicine's role in modulating these biomarkers.

Conclusions:

• Computational analysis provides evidence for colchicine's inhibitory role against MMP-9, NOX2, and TGF-β1.
• These findings suggest colchicine may be a therapeutic agent to inhibit cardiac remodeling post-MI, potentially reducing heart failure incidence.