Inhibitory effect of quercetin on matrix metalloproteinase 9 activity Molecular mechanism and structure-activity relationship of the flavonoid-enzyme interaction

Autores
Saragusti, Alejandra Cristina; Ortega, María Gabriela; Cabrera, Jose Luis; Estrin, Dario Ariel; Marti, Marcelo Adrian; Chiabrando, Gustavo Alberto
Año de publicación
2010
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Epidemiological studies have demonstrated an inverse association between the consumption of flavonoid-rich 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-activity relationship of the inhibitory effect of flavonoids on MMP-9 activity. We show that quercetin inhibited MMP-9 activity with an IC50 value of 22μM. By using docking and molecular dynamics simulations, it was shown that quercetin interacted in the S1' subsite of the MMP-9 active site. Moreover, the structure-activity relationship analysis demonstrated that flavonoid R3'-OH and R4'-OH 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. © 2010 Elsevier B.V.
Fil: Saragusti, Alejandra Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Bioquímica Clínica; Argentina
Fil: Ortega, María Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacia; Argentina
Fil: Cabrera, Jose Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacia; Argentina
Fil: Estrin, Dario Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentina
Fil: Marti, Marcelo Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Inorgánica, Analítica y Química Física; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina
Fil: Chiabrando, Gustavo Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Bioquímica Clínica; Argentina
Materia
Diet Polyphenol
Docking
Flavonoid
Molecular Dynamics
Zymography
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/71392
Acceder
id CONICETDig_cf9ee65ff617b115f399cd64a9696526
oai_identifier_str oai:ri.conicet.gov.ar:11336/71392
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Inhibitory effect of quercetin on matrix metalloproteinase 9 activity Molecular mechanism and structure-activity relationship of the flavonoid-enzyme interactionSaragusti, Alejandra CristinaOrtega, María GabrielaCabrera, Jose LuisEstrin, Dario ArielMarti, Marcelo AdrianChiabrando, Gustavo AlbertoDiet PolyphenolDockingFlavonoidMolecular DynamicsZymographyhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Epidemiological studies have demonstrated an inverse association between the consumption of flavonoid-rich 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-activity relationship of the inhibitory effect of flavonoids on MMP-9 activity. We show that quercetin inhibited MMP-9 activity with an IC50 value of 22μM. By using docking and molecular dynamics simulations, it was shown that quercetin interacted in the S1' subsite of the MMP-9 active site. Moreover, the structure-activity relationship analysis demonstrated that flavonoid R3'-OH and R4'-OH 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. © 2010 Elsevier B.V.Fil: Saragusti, Alejandra Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Bioquímica Clínica; ArgentinaFil: Ortega, María Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacia; ArgentinaFil: Cabrera, Jose Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacia; ArgentinaFil: Estrin, Dario Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; ArgentinaFil: Marti, Marcelo Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Inorgánica, Analítica y Química Física; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; ArgentinaFil: Chiabrando, Gustavo Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Bioquímica Clínica; ArgentinaElsevier Science2010-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/71392Saragusti, Alejandra Cristina; Ortega, María Gabriela; Cabrera, Jose Luis; Estrin, Dario Ariel; Marti, Marcelo Adrian; et al.; Inhibitory effect of quercetin on matrix metalloproteinase 9 activity Molecular mechanism and structure-activity relationship of the flavonoid-enzyme interaction; Elsevier Science; European Journal of Pharmacology; 644; 1-3; 10-2010; 138-1450014-2999CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0014299910006643info:eu-repo/semantics/altIdentifier/doi/10.1016/j.ejphar.2010.07.001info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T11:09:51Zoai:ri.conicet.gov.ar:11336/71392instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-22 11:09:52.264CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Inhibitory effect of quercetin on matrix metalloproteinase 9 activity Molecular mechanism and structure-activity relationship of the flavonoid-enzyme interaction
title Inhibitory effect of quercetin on matrix metalloproteinase 9 activity Molecular mechanism and structure-activity relationship of the flavonoid-enzyme interaction
spellingShingle Inhibitory effect of quercetin on matrix metalloproteinase 9 activity Molecular mechanism and structure-activity relationship of the flavonoid-enzyme interaction
Saragusti, Alejandra Cristina
Diet Polyphenol
Docking
Flavonoid
Molecular Dynamics
Zymography
title_short Inhibitory effect of quercetin on matrix metalloproteinase 9 activity Molecular mechanism and structure-activity relationship of the flavonoid-enzyme interaction
title_full Inhibitory effect of quercetin on matrix metalloproteinase 9 activity Molecular mechanism and structure-activity relationship of the flavonoid-enzyme interaction
title_fullStr Inhibitory effect of quercetin on matrix metalloproteinase 9 activity Molecular mechanism and structure-activity relationship of the flavonoid-enzyme interaction
title_full_unstemmed Inhibitory effect of quercetin on matrix metalloproteinase 9 activity Molecular mechanism and structure-activity relationship of the flavonoid-enzyme interaction
title_sort Inhibitory effect of quercetin on matrix metalloproteinase 9 activity Molecular mechanism and structure-activity relationship of the flavonoid-enzyme interaction
dc.creator.none.fl_str_mv Saragusti, Alejandra Cristina
Ortega, María Gabriela
Cabrera, Jose Luis
Estrin, Dario Ariel
Marti, Marcelo Adrian
Chiabrando, Gustavo Alberto
author Saragusti, Alejandra Cristina
author_facet Saragusti, Alejandra Cristina
Ortega, María Gabriela
Cabrera, Jose Luis
Estrin, Dario Ariel
Marti, Marcelo Adrian
Chiabrando, Gustavo Alberto
author_role author
author2 Ortega, María Gabriela
Cabrera, Jose Luis
Estrin, Dario Ariel
Marti, Marcelo Adrian
Chiabrando, Gustavo Alberto
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Diet Polyphenol
Docking
Flavonoid
Molecular Dynamics
Zymography
topic Diet Polyphenol
Docking
Flavonoid
Molecular Dynamics
Zymography
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Epidemiological studies have demonstrated an inverse association between the consumption of flavonoid-rich 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-activity relationship of the inhibitory effect of flavonoids on MMP-9 activity. We show that quercetin inhibited MMP-9 activity with an IC50 value of 22μM. By using docking and molecular dynamics simulations, it was shown that quercetin interacted in the S1' subsite of the MMP-9 active site. Moreover, the structure-activity relationship analysis demonstrated that flavonoid R3'-OH and R4'-OH 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. © 2010 Elsevier B.V.
Fil: Saragusti, Alejandra Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Bioquímica Clínica; Argentina
Fil: Ortega, María Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacia; Argentina
Fil: Cabrera, Jose Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacia; Argentina
Fil: Estrin, Dario Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentina
Fil: Marti, Marcelo Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Inorgánica, Analítica y Química Física; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina
Fil: Chiabrando, Gustavo Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Bioquímica Clínica; Argentina
description Epidemiological studies have demonstrated an inverse association between the consumption of flavonoid-rich 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-activity relationship of the inhibitory effect of flavonoids on MMP-9 activity. We show that quercetin inhibited MMP-9 activity with an IC50 value of 22μM. By using docking and molecular dynamics simulations, it was shown that quercetin interacted in the S1' subsite of the MMP-9 active site. Moreover, the structure-activity relationship analysis demonstrated that flavonoid R3'-OH and R4'-OH 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. © 2010 Elsevier B.V.
publishDate 2010
dc.date.none.fl_str_mv 2010-10
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/71392
Saragusti, Alejandra Cristina; Ortega, María Gabriela; Cabrera, Jose Luis; Estrin, Dario Ariel; Marti, Marcelo Adrian; et al.; Inhibitory effect of quercetin on matrix metalloproteinase 9 activity Molecular mechanism and structure-activity relationship of the flavonoid-enzyme interaction; Elsevier Science; European Journal of Pharmacology; 644; 1-3; 10-2010; 138-145
0014-2999
CONICET Digital
CONICET
url http://hdl.handle.net/11336/71392
identifier_str_mv Saragusti, Alejandra Cristina; Ortega, María Gabriela; Cabrera, Jose Luis; Estrin, Dario Ariel; Marti, Marcelo Adrian; et al.; Inhibitory effect of quercetin on matrix metalloproteinase 9 activity Molecular mechanism and structure-activity relationship of the flavonoid-enzyme interaction; Elsevier Science; European Journal of Pharmacology; 644; 1-3; 10-2010; 138-145
0014-2999
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0014299910006643
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.ejphar.2010.07.001
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
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eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier Science
publisher.none.fl_str_mv Elsevier Science
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instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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