Elucidating the Anti-Metastatic Potency of Morinda citrifolia L. Compounds via Targeting MMP9: An integrative Network Pharmacology and Molecular Dynamics simulation

Metastasis is a major cause of mortality in breast cancer, making it a critical target in therapeutic strategies. Morinda citrifolia L., a tropical medicinal plant, has shown promise due to its bioactive compounds. This study investigates the anti-metastatic potential of M. citrifolia compounds by targeting matrix metalloproteinase-9 (MMP-9), a key protein involved in tumor invasion and metastasis. An integrative in silico approach was employed, including drug-likeness and toxicity screening, biological activity prediction, membrane permeability analysis, target protein identification, enrichment analysis, protein structure validation, molecular docking, and molecular dynamics simulations. Among the screened compounds, quercetin and obtusin exhibited strong binding affinity for MMP-9. We suggest that quercetin inhibits MMP-9 via zinc chelation and multi-point hydrogen bonding, while obtusin acts through cavity remodeling and potential allosteric modulation. Both compounds overlap with Marimastat's binding site, an established MMP-9 inhibitor, but engage the enzyme through distinct molecular interactions, highlighting their complementary mechanisms. Quercetin and obtusin from M. citrifolia inhibit MMP-9 through different yet complementary modes of action, suggesting their potential as anti-metastatic agents. These findings support further investigation through in vitro and in vivo studies to validate their therapeutic efficacy.