Among others polyphenols, quercetin is one of the most commonly flavonoid found in
human diet. Increased activity of matrix metalloproteinases (MMPs) has been
implicated in the development and progression of atherosclerotic lesions,
especially the gelatinase MMP-9. Although it has been reported the inhibitory effect of
certain polyphenols on MMP activity, the molecular mechanisms of this inhibition are
still unknown. Herein we first evaluate the inhibitory effect of quercetin on the active
MMP-9 by zimography assays and secondly we determine the most probable sites of
quercetin interaction with the MMP-9 catalytic domain using a combination of
docking techniques and molecular dynamics (MD) simulations. By zymography assays we showed that this flavonoid inhibits the enzyme activity in a dose and time dependent
manner with an IC50 of 54.0 ± 3.3 ìM. In addition, the evaluation of possible interaction sites between quercetin and MMP-9 demonstrated that quercetin may bind to different subsites of the enzyme active site. The results revealed five possible quercetin-MMP-9 complex structures where quercetin is stabilized in the MMP-9 active site by hydrophobic interactions and hydrogen bonds involving flavonoid hydroxyls and enzyme residues.