Articles producció científica> Bioquímica i Biotecnologia

Identification of Broad-Spectrum MMP Inhibitors by Virtual Screening

  • Datos identificativos

    Identificador: imarina:9225823
    Autores:
    Gimeno, AleixCuffaro, DorettaNuti, ElisaOjeda-Montes, Maria JoseBeltran-Debon, RaulMulero, MiquelRossello, ArmandoPujadas, GerardGarcia-Vallve, Santiago
    Resumen:
    Matrix metalloproteinases (MMPs) are the family of proteases that are mainly responsible for degrading extracellular matrix (ECM) components. In the skin, the overexpression of MMPs as a result of ultraviolet radiation triggers an imbalance in the ECM turnover in a process called photoaging, which ultimately results in skin wrinkling and premature skin ageing. Therefore, the inhibition of different enzymes of the MMP family at a topical level could have positive implications for photoaging. Considering that the MMP catalytic region is mostly conserved across different enzymes of the MMP family, in this study we aimed to design a virtual screening (VS) workflow to identify broad-spectrum MMP inhibitors that can be used to delay the development of photoaging. Our in silico approach was validated in vitro with 20 VS hits from the Specs library that were not only structurally different from one another but also from known MMP inhibitors. In this bioactivity assay, 18 of the 20 compounds inhibit at least one of the assayed MMPs at 100 mu M (with 5 of them showing around 50% inhibition in all the tested MMPs at this concentration). Finally, this VS was used to identify natural products that have the potential to act as broad-spectrum MMP inhibitors and be used as a treatment for photoaging.
  • Otros:

    Autor según el artículo: Gimeno, Aleix; Cuffaro, Doretta; Nuti, Elisa; Ojeda-Montes, Maria Jose; Beltran-Debon, Raul; Mulero, Miquel; Rossello, Armando; Pujadas, Gerard; Garcia-Vallve, Santiago;
    Departamento: Bioquímica i Biotecnologia
    Autor/es de la URV: Beltrán Debón, Raúl Alejandro / Garcia Vallve, Santiago / Mulero Abellán, Miguel / OJEDA MONTES, Mª JOSÉ / Pujadas Anguiano, Gerard
    Palabras clave: Trials Therapy Skin treatment Photoaging Non-selective matrix metalloproteinases Natural products Matrix-metalloproteinase inhibitors Inflammatory-bowel-disease In vitro validation Expression Discovery Design Database Crystal-structures Cancer Bioactivity prediction
    Resumen: Matrix metalloproteinases (MMPs) are the family of proteases that are mainly responsible for degrading extracellular matrix (ECM) components. In the skin, the overexpression of MMPs as a result of ultraviolet radiation triggers an imbalance in the ECM turnover in a process called photoaging, which ultimately results in skin wrinkling and premature skin ageing. Therefore, the inhibition of different enzymes of the MMP family at a topical level could have positive implications for photoaging. Considering that the MMP catalytic region is mostly conserved across different enzymes of the MMP family, in this study we aimed to design a virtual screening (VS) workflow to identify broad-spectrum MMP inhibitors that can be used to delay the development of photoaging. Our in silico approach was validated in vitro with 20 VS hits from the Specs library that were not only structurally different from one another but also from known MMP inhibitors. In this bioactivity assay, 18 of the 20 compounds inhibit at least one of the assayed MMPs at 100 mu M (with 5 of them showing around 50% inhibition in all the tested MMPs at this concentration). Finally, this VS was used to identify natural products that have the potential to act as broad-spectrum MMP inhibitors and be used as a treatment for photoaging.
    Áreas temáticas: Zootecnia / recursos pesqueiros Saúde coletiva Química Psicología Planejamento urbano e regional / demografia Physical and theoretical chemistry Pharmaceutical science Organic chemistry Odontología Nutrição Molecular medicine Medicine (miscellaneous) Medicina veterinaria Medicina iii Medicina ii Medicina i Materiais Matemática / probabilidade e estatística Interdisciplinar Geografía General medicine Farmacia Ensino Engenharias iv Engenharias iii Engenharias ii Engenharias i Educação física Economia Drug discovery Ciências biológicas iii Ciências biológicas ii Ciências biológicas i Ciências ambientais Ciências agrárias i Ciência de alimentos Ciência da computação Chemistry, organic Chemistry, multidisciplinary Chemistry (miscellaneous) Biotecnología Biodiversidade Biochemistry & molecular biology Astronomia / física Analytical chemistry
    Acceso a la licencia de uso: https://creativecommons.org/licenses/by/3.0/es/
    Direcció de correo del autor: miquel.mulero@urv.cat santi.garcia-vallve@urv.cat gerard.pujadas@urv.cat raul.beltran@urv.cat
    Identificador del autor: 0000-0002-0348-7497 0000-0003-2598-8089 0000-0001-9691-1906
    Fecha de alta del registro: 2024-07-27
    Volumen de revista: 26
    Versión del articulo depositado: info:eu-repo/semantics/publishedVersion
    Enlace a la fuente original: https://www.mdpi.com/1420-3049/26/15/4553
    URL Documento de licencia: https://repositori.urv.cat/ca/proteccio-de-dades/
    Referencia al articulo segun fuente origial: Molecules. 26 (15):
    Referencia de l'ítem segons les normes APA: Gimeno, Aleix; Cuffaro, Doretta; Nuti, Elisa; Ojeda-Montes, Maria Jose; Beltran-Debon, Raul; Mulero, Miquel; Rossello, Armando; Pujadas, Gerard; Garci (2021). Identification of Broad-Spectrum MMP Inhibitors by Virtual Screening. Molecules, 26(15), -. DOI: 10.3390/molecules26154553
    DOI del artículo: 10.3390/molecules26154553
    Entidad: Universitat Rovira i Virgili
    Año de publicación de la revista: 2021
    Tipo de publicación: Journal Publications
  • Palabras clave:

    Analytical Chemistry,Biochemistry & Molecular Biology,Chemistry (Miscellaneous),Chemistry, Multidisciplinary,Chemistry, Organic,Drug Discovery,Medicine (Miscellaneous),Molecular Medicine,Organic Chemistry,Pharmaceutical Science,Physical and Theoretical Chemistry
    Trials
    Therapy
    Skin treatment
    Photoaging
    Non-selective matrix metalloproteinases
    Natural products
    Matrix-metalloproteinase inhibitors
    Inflammatory-bowel-disease
    In vitro validation
    Expression
    Discovery
    Design
    Database
    Crystal-structures
    Cancer
    Bioactivity prediction
    Zootecnia / recursos pesqueiros
    Saúde coletiva
    Química
    Psicología
    Planejamento urbano e regional / demografia
    Physical and theoretical chemistry
    Pharmaceutical science
    Organic chemistry
    Odontología
    Nutrição
    Molecular medicine
    Medicine (miscellaneous)
    Medicina veterinaria
    Medicina iii
    Medicina ii
    Medicina i
    Materiais
    Matemática / probabilidade e estatística
    Interdisciplinar
    Geografía
    General medicine
    Farmacia
    Ensino
    Engenharias iv
    Engenharias iii
    Engenharias ii
    Engenharias i
    Educação física
    Economia
    Drug discovery
    Ciências biológicas iii
    Ciências biológicas ii
    Ciências biológicas i
    Ciências ambientais
    Ciências agrárias i
    Ciência de alimentos
    Ciência da computação
    Chemistry, organic
    Chemistry, multidisciplinary
    Chemistry (miscellaneous)
    Biotecnología
    Biodiversidade
    Biochemistry & molecular biology
    Astronomia / física
    Analytical chemistry
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