CIBICI   14215
CENTRO DE INVESTIGACION EN BIOQUIMICA CLINICA E INMUNOLOGIA
Unidad Ejecutora - UE
artículos
Título:
Inhibitory effect of quercetin on matrix metalloproteinase 9 activity Molecular
Autor/es:
SARAGUSTI A; ORTEGA G; CABRERA JL; ESTRIN DA; MARTI MA; CHIABRANDO GA
Revista:
EUROPEAN JOURNAL OF PHARMACOLOGY
Editorial:
ELSEVIER SCIENCE BV
Referencias:
Año: 2010 vol. 644 p. 138 - 145
ISSN:
0014-2999
Resumen:
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.