Author, as appears in the article.: Gimeno, Aleix; Cuffaro, Doretta; Nuti, Elisa; Ojeda-Montes, Maria Jose; Beltran-Debon, Raul; Mulero, Miquel; Rossello, Armando; Pujadas, Gerard; Garcia-Vallve, Santiago;

Department: Bioquímica i Biotecnologia

URV's Author/s: Beltrán Debón, Raúl Alejandro / Garcia Vallve, Santiago / Mulero Abellán, Miguel / OJEDA MONTES, Mª JOSÉ / Pujadas Anguiano, Gerard

Keywords: 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

Abstract: 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.

Thematic Areas: 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

licence for use: https://creativecommons.org/licenses/by/3.0/es/

Author's mail: raul.beltran@urv.cat gerard.pujadas@urv.cat santi.garcia-vallve@urv.cat miquel.mulero@urv.cat

Author identifier: 0000-0001-9691-1906 0000-0003-2598-8089 0000-0002-0348-7497

Record's date: 2023-02-19

Journal volume: 26

Papper version: info:eu-repo/semantics/publishedVersion

Link to the original source: https://www.mdpi.com/1420-3049/26/15/4553

Licence document URL: http://repositori.urv.cat/ca/proteccio-de-dades/

Papper original source: Molecules. 26 (15):

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

Article's DOI: 10.3390/molecules26154553

Entity: Universitat Rovira i Virgili

Journal publication year: 2021

Publication Type: Journal Publications