Oxaprozin: A new hope in the modulation of matrix metalloproteinase 9 activity.

ABSTRACT

Oxaprozin (4,5-diphenyl-2-oxazolepropionic acid) is a non-steroidal, analgesic and antipyretic propionic acid derivative, whose activity in treating inflammatory disorders is well known. The aim of this study was to investigate the ability of oxaprozin to modulate the activity of matrix metalloproteinase 9 (MMP-9), a zinc-dependent endopeptidase involved in a wide range of physiological and pathological events associated with extracellular matrix (ECM) remodelling. The interaction between oxaprozin and MMP-9 was firstly investigated in silico by molecular docking and analysis with LIGPLOT software. Subsequently, the potential inhibitory activity of oxaprozin against MMP-9 and the possible mechanism of the ligand-enzyme interaction were investigated in vitro. Taking into account the in silico findings, MMP-9 can be considered a potential target of oxaprozin, which seems to be able to chelate the catalytic zinc ion through the nitrogen of the oxazole ring and the carboxylate moiety. Moreover, one of the phenyl rings interact with the S1' inhibitor-binding pocket through hydrophobic interaction. Gelatin zymography and enzymatic inhibition assay confirmed the potential role of oxaprozin as a competitive inhibitor of MMP-9. These observations sound particularly interesting if we consider the pathological role of MMP-9, especially evident in inflammatory conditions and cancer. This work may represent a starting point to improve the understanding of the role of oxaprozin, as well as its structural analogues, in modulating the MMP-9 function.