CONICET | Buscador de Institutos y Recursos Humanos

Epidemiological studies have demonstrated an inverse association between the consumption of flavonoidrich diets and the risk of atherosclerosis. In addition, an increased activity of the matrix metalloproteinase 9 (MMP-9) has been implicated in the development and progression of atherosclerotic lesions. Even though the relationship between flavonoid chemical structure and the inhibitory property on MMP activity has been established, the molecular mechanisms of this inhibition are still unknown. Herein, we first evaluated the inhibitory effect of quercetin on MMP-9 activity by zymography and a fluorescent gelatin dequenching assay, secondly we determined the most probable sites and modes of quercetin interaction with the MMP-9 catalytic domain by using molecular modelling techniques, and finally, we investigated the structure¨Cactivity relationship of the inhibitory effect of flavonoids on MMP-9 activity. We show that quercetin inhibited MMP- 9 activity with an IC50 value of 22 ¦ÌM. By using docking and molecular dynamics simulations, it was shown that quercetin interacted in the S1¡ä subsite of the MMP-9 active site. Moreover, the structure¨Cactivity relationship analysis demonstrated that flavonoid R3¡ä¨COH and R4¡ä¨COH substitutions were relevant to the inhibitory property against MMP-9 activity. In conclusion, our data constitute the first evidence about the quercetin and MMP-9 interaction, suggesting a mechanism to explain the inhibitory effect of the flavonoid on the enzymatic activity of MMP-9, which provides an additional molecular target for the cardioprotective activity of quercetin.flavonoidrich diets and the risk of atherosclerosis. In addition, an increased activity of the matrix metalloproteinase 9 (MMP-9) has been implicated in the development and progression of atherosclerotic lesions. Even though the relationship between flavonoid chemical structure and the inhibitory property on MMP activity has been established, the molecular mechanisms of this inhibition are still unknown. Herein, we first evaluated the inhibitory effect of quercetin on MMP-9 activity by zymography and a fluorescent gelatin dequenching assay, secondly we determined the most probable sites and modes of quercetin interaction with the MMP-9 catalytic domain by using molecular modelling techniques, and finally, we investigated the structure¨Cactivity relationship of the inhibitory effect of flavonoids on MMP-9 activity. We show that quercetin inhibited MMP- 9 activity with an IC50 value of 22 ¦ÌM. By using docking and molecular dynamics simulations, it was shown that quercetin interacted in the S1¡ä subsite of the MMP-9 active site. Moreover, the structure¨Cactivity relationship analysis demonstrated that flavonoid R3¡ä¨COH and R4¡ä¨COH substitutions were relevant to the inhibitory property against MMP-9 activity. In conclusion, our data constitute the first evidence about the quercetin and MMP-9 interaction, suggesting a mechanism to explain the inhibitory effect of the flavonoid on the enzymatic activity of MMP-9, which provides an additional molecular target for the cardioprotective activity of quercetin.flavonoid chemical structure and the inhibitory property on MMP activity has been established, the molecular mechanisms of this inhibition are still unknown. Herein, we first evaluated the inhibitory effect of quercetin on MMP-9 activity by zymography and a fluorescent gelatin dequenching assay, secondly we determined the most probable sites and modes of quercetin interaction with the MMP-9 catalytic domain by using molecular modelling techniques, and finally, we investigated the structure¨Cactivity relationship of the inhibitory effect of flavonoids on MMP-9 activity. We show that quercetin inhibited MMP- 9 activity with an IC50 value of 22 ¦ÌM. By using docking and molecular dynamics simulations, it was shown that quercetin interacted in the S1¡ä subsite of the MMP-9 active site. Moreover, the structure¨Cactivity relationship analysis demonstrated that flavonoid R3¡ä¨COH and R4¡ä¨COH substitutions were relevant to the inhibitory property against MMP-9 activity. In conclusion, our data constitute the first evidence about the quercetin and MMP-9 interaction, suggesting a mechanism to explain the inhibitory effect of the flavonoid on the enzymatic activity of MMP-9, which provides an additional molecular target for the cardioprotective activity of quercetin.first evaluated the inhibitory effect of quercetin on MMP-9 activity by zymography and a fluorescent gelatin dequenching assay, secondly we determined the most probable sites and modes of quercetin interaction with the MMP-9 catalytic domain by using molecular modelling techniques, and finally, we investigated the structure¨Cactivity relationship of the inhibitory effect of flavonoids on MMP-9 activity. We show that quercetin inhibited MMP- 9 activity with an IC50 value of 22 ¦ÌM. By using docking and molecular dynamics simulations, it was shown that quercetin interacted in the S1¡ä subsite of the MMP-9 active site. Moreover, the structure¨Cactivity relationship analysis demonstrated that flavonoid R3¡ä¨COH and R4¡ä¨COH substitutions were relevant to the inhibitory property against MMP-9 activity. In conclusion, our data constitute the first evidence about the quercetin and MMP-9 interaction, suggesting a mechanism to explain the inhibitory effect of the flavonoid on the enzymatic activity of MMP-9, which provides an additional molecular target for the cardioprotective activity of quercetin.fluorescent gelatin dequenching assay, secondly we determined the most probable sites and modes of quercetin interaction with the MMP-9 catalytic domain by using molecular modelling techniques, and finally, we investigated the structure¨Cactivity relationship of the inhibitory effect of flavonoids on MMP-9 activity. We show that quercetin inhibited MMP- 9 activity with an IC50 value of 22 ¦ÌM. By using docking and molecular dynamics simulations, it was shown that quercetin interacted in the S1¡ä subsite of the MMP-9 active site. Moreover, the structure¨Cactivity relationship analysis demonstrated that flavonoid R3¡ä¨COH and R4¡ä¨COH substitutions were relevant to the inhibitory property against MMP-9 activity. In conclusion, our data constitute the first evidence about the quercetin and MMP-9 interaction, suggesting a mechanism to explain the inhibitory effect of the flavonoid on the enzymatic activity of MMP-9, which provides an additional molecular target for the cardioprotective activity of quercetin.finally, we investigated the structure¨Cactivity relationship of the inhibitory effect of flavonoids on MMP-9 activity. We show that quercetin inhibited MMP- 9 activity with an IC50 value of 22 ¦ÌM. By using docking and molecular dynamics simulations, it was shown that quercetin interacted in the S1¡ä subsite of the MMP-9 active site. Moreover, the structure¨Cactivity relationship analysis demonstrated that flavonoid R3¡ä¨COH and R4¡ä¨COH substitutions were relevant to the inhibitory property against MMP-9 activity. In conclusion, our data constitute the first evidence about the quercetin and MMP-9 interaction, suggesting a mechanism to explain the inhibitory effect of the flavonoid on the enzymatic activity of MMP-9, which provides an additional molecular target for the cardioprotective activity of quercetin.flavonoids on MMP-9 activity. We show that quercetin inhibited MMP- 9 activity with an IC50 value of 22 ¦ÌM. By using docking and molecular dynamics simulations, it was shown that quercetin interacted in the S1¡ä subsite of the MMP-9 active site. Moreover, the structure¨Cactivity relationship analysis demonstrated that flavonoid R3¡ä¨COH and R4¡ä¨COH substitutions were relevant to the inhibitory property against MMP-9 activity. In conclusion, our data constitute the first evidence about the quercetin and MMP-9 interaction, suggesting a mechanism to explain the inhibitory effect of the flavonoid on the enzymatic activity of MMP-9, which provides an additional molecular target for the cardioprotective activity of quercetin.50 value of 22 ¦ÌM. By using docking and molecular dynamics simulations, it was shown that quercetin interacted in the S1¡ä subsite of the MMP-9 active site. Moreover, the structure¨Cactivity relationship analysis demonstrated that flavonoid R3¡ä¨COH and R4¡ä¨COH substitutions were relevant to the inhibitory property against MMP-9 activity. In conclusion, our data constitute the first evidence about the quercetin and MMP-9 interaction, suggesting a mechanism to explain the inhibitory effect of the flavonoid on the enzymatic activity of MMP-9, which provides an additional molecular target for the cardioprotective activity of quercetin.¡ä subsite of the MMP-9 active site. Moreover, the structure¨Cactivity relationship analysis demonstrated that flavonoid R3¡ä¨COH and R4¡ä¨COH substitutions were relevant to the inhibitory property against MMP-9 activity. In conclusion, our data constitute the first evidence about the quercetin and MMP-9 interaction, suggesting a mechanism to explain the inhibitory effect of the flavonoid on the enzymatic activity of MMP-9, which provides an additional molecular target for the cardioprotective activity of quercetin.flavonoid R3¡ä¨COH and R4¡ä¨COH substitutions were relevant to the inhibitory property against MMP-9 activity. In conclusion, our data constitute the first evidence about the quercetin and MMP-9 interaction, suggesting a mechanism to explain the inhibitory effect of the flavonoid on the enzymatic activity of MMP-9, which provides an additional molecular target for the cardioprotective activity of quercetin.first evidence about the quercetin and MMP-9 interaction, suggesting a mechanism to explain the inhibitory effect of the flavonoid on the enzymatic activity of MMP-9, which provides an additional molecular target for the cardioprotective activity of quercetin.flavonoid on the enzymatic activity of MMP-9, which provides an additional molecular target for the cardioprotective activity of quercetin.