Inhibitory effect of quercetin on the matrix metalloproteinase 9 activity. Molecular mechanism

ALEJANDRA C. SARAGUSTI; MARÍA G. ORTEGA; JOSÉ L. CABRERA; DARÍO A. ESTRIN,; MARCELO A. MARTI,; GUSTAVO A. CHIABRANDO.

ELSEVIER SCIENCE BV

Año: 2010 vol. 644 p. 146 - 146

font size="3" face="Cambria"> Epidemiological studies suggest that the consumption of flavonoid-rich diets decreases the risk of cardiovascular diseases, but the protective mechanisms are not known. Increased activity of the matrix metalloproteinase 9 (MMP-9) has been implicated in the development and progression of atherosclerotic lesions. Herein we first evaluate the inhibitory effect of quercetin on the MMP-9 activity by fluorescent gelatin dequenching assay, secondly we determine the most probable sites and modes of quercetin interaction with the MMP-9 catalytic domain using a combination of docking and molecular dynamics (MD) simulation, and finally, we investigate the structural activity relationships (SARs) of the quercetin inhibition on the MMP-9 activity using quercetin structural analogs. We showed that quercetin inhibits the MMP-9 activity with an IC50 value of 22 ìM. Docking and MD simulation results revealed two most probable