In Silico and In Vitro Approach for Validating the Inhibition of Matrix Metalloproteinase-9 by Quercetin
Abstract
PURPOSE: To validate the mechanism and inhibitory activity of quercetin against matrix metalloproteinase-9 (MMP-9) using a hybrid in silico and in vitro approach. METHODS: The structure of MMP-9 was obtained from the Protein Data Bank, and the active site was identified using previous annotations from the Universal Protein Resource. The structure of quercetin was obtained from ZINC15. Molecular docking was performed to quantify the binding affinity of quercetin to the active site of MMP-9. The inhibitory effect of various concentrations of quercetin (0.0025, 0.025, 0.25, 1.0, and 1.5 mM) on MMP-9 was quantified using a commercially available fluorometric assay. The cytotoxicity of quercetin to immortalized human corneal epithelial cells (HCECs) was quantified by obtaining the metabolic activities of the cells exposed to various concentrations of quercetin for 24 hr. RESULTS: Quercetin interacts with MMP-9 by binding within the active site pocket and interacting with residues LEU 188, ALA 189, GLU 227, and MET 247. The binding affinity predicted by molecular docking was -9.9 kcal/mol. All concentrations of quercetin demonstrated significant inhibition of MMP-9 enzyme activity (all P 0.99). CONCLUSIONS: Quercetin inhibited MMP-9 in a dose-dependent manner and was well-tolerated by HCECs, suggesting a potential role in therapy for diseases with upregulated MMP-9 as part of its pathogenesis.
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