Identification of Broad-Spectrum MMP Inhibitors by Virtual Screening
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 u...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-07-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/26/15/4553 |
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| author | Aleix Gimeno Doretta Cuffaro Elisa Nuti María José Ojeda-Montes Raúl Beltrán-Debón Miquel Mulero Armando Rossello Gerard Pujadas Santiago Garcia-Vallvé |
| author_facet | Aleix Gimeno Doretta Cuffaro Elisa Nuti María José Ojeda-Montes Raúl Beltrán-Debón Miquel Mulero Armando Rossello Gerard Pujadas Santiago Garcia-Vallvé |
| author_sort | Aleix Gimeno |
| collection | DOAJ |
| description | 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 μM (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. |
| first_indexed | 2024-03-10T09:10:53Z |
| format | Article |
| id | doaj.art-329fb1eec2ae4d9097a4f3ca6842d0f7 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T09:10:53Z |
| publishDate | 2021-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-329fb1eec2ae4d9097a4f3ca6842d0f72023-11-22T05:59:47ZengMDPI AGMolecules1420-30492021-07-012615455310.3390/molecules26154553Identification of Broad-Spectrum MMP Inhibitors by Virtual ScreeningAleix Gimeno0Doretta Cuffaro1Elisa Nuti2María José Ojeda-Montes3Raúl Beltrán-Debón4Miquel Mulero5Armando Rossello6Gerard Pujadas7Santiago Garcia-Vallvé8Research Group in Cheminformatics & Nutrition, Departament de Bioquímica i Biotecnologia, Campus de Sescelades, Universitat Rovira i Virgili, 43007 Tarragona, Catalonia, SpainDepartment of Pharmacy, University of Pisa, Via Bonanno 6, 56126 Pisa, ItalyDepartment of Pharmacy, University of Pisa, Via Bonanno 6, 56126 Pisa, ItalyResearch Group in Cheminformatics & Nutrition, Departament de Bioquímica i Biotecnologia, Campus de Sescelades, Universitat Rovira i Virgili, 43007 Tarragona, Catalonia, SpainResearch Group in Cheminformatics & Nutrition, Departament de Bioquímica i Biotecnologia, Campus de Sescelades, Universitat Rovira i Virgili, 43007 Tarragona, Catalonia, SpainResearch Group in Cheminformatics & Nutrition, Departament de Bioquímica i Biotecnologia, Campus de Sescelades, Universitat Rovira i Virgili, 43007 Tarragona, Catalonia, SpainDepartment of Pharmacy, University of Pisa, Via Bonanno 6, 56126 Pisa, ItalyResearch Group in Cheminformatics & Nutrition, Departament de Bioquímica i Biotecnologia, Campus de Sescelades, Universitat Rovira i Virgili, 43007 Tarragona, Catalonia, SpainResearch Group in Cheminformatics & Nutrition, Departament de Bioquímica i Biotecnologia, Campus de Sescelades, Universitat Rovira i Virgili, 43007 Tarragona, Catalonia, SpainMatrix 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 μM (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.https://www.mdpi.com/1420-3049/26/15/4553photoagingskin treatmentnon-selective matrix metalloproteinasesnatural productsbioactivity predictionin vitro validation |
| spellingShingle | Aleix Gimeno Doretta Cuffaro Elisa Nuti María José Ojeda-Montes Raúl Beltrán-Debón Miquel Mulero Armando Rossello Gerard Pujadas Santiago Garcia-Vallvé Identification of Broad-Spectrum MMP Inhibitors by Virtual Screening Molecules photoaging skin treatment non-selective matrix metalloproteinases natural products bioactivity prediction in vitro validation |
| title | Identification of Broad-Spectrum MMP Inhibitors by Virtual Screening |
| title_full | Identification of Broad-Spectrum MMP Inhibitors by Virtual Screening |
| title_fullStr | Identification of Broad-Spectrum MMP Inhibitors by Virtual Screening |
| title_full_unstemmed | Identification of Broad-Spectrum MMP Inhibitors by Virtual Screening |
| title_short | Identification of Broad-Spectrum MMP Inhibitors by Virtual Screening |
| title_sort | identification of broad spectrum mmp inhibitors by virtual screening |
| topic | photoaging skin treatment non-selective matrix metalloproteinases natural products bioactivity prediction in vitro validation |
| url | https://www.mdpi.com/1420-3049/26/15/4553 |
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