{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T08:47:45Z","timestamp":1782377265053,"version":"3.54.5"},"reference-count":52,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2023,7,4]],"date-time":"2023-07-04T00:00:00Z","timestamp":1688428800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Pisa","award":["PRA_2020_58"],"award-info":[{"award-number":["PRA_2020_58"]}]},{"name":"University of Pisa","award":["2015FI_B00655"],"award-info":[{"award-number":["2015FI_B00655"]}]},{"name":"Catalonia Government","award":["PRA_2020_58"],"award-info":[{"award-number":["PRA_2020_58"]}]},{"name":"Catalonia Government","award":["2015FI_B00655"],"award-info":[{"award-number":["2015FI_B00655"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Matrix metalloproteinase 13 plays a central role in osteoarthritis (OA), as its overexpression induces an excessive breakdown of collagen that results in an imbalance between collagen synthesis and degradation in the joint, leading to progressive articular cartilage degradation. Therefore, MMP-13 has been proposed as a key therapeutic target for OA. Here we have developed a virtual screening workflow aimed at identifying selective non-zinc-binding MMP-13 inhibitors by targeting the deep S1\u2032 pocket of MMP-13. Three ligands were found to inhibit MMP-13 in the \u00b5M range, and one of these showed selectivity over other MMPs. A structure-based analysis guided the chemical optimization of the hit compound, leading to the obtaining of a new N-acyl hydrazone-based derivative with improved inhibitory activity and selectivity for the target enzyme.<\/jats:p>","DOI":"10.3390\/ijms241311098","type":"journal-article","created":{"date-parts":[[2023,7,5]],"date-time":"2023-07-05T00:33:42Z","timestamp":1688517222000},"page":"11098","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Identification of N-Acyl Hydrazones as New Non-Zinc-Binding MMP-13 Inhibitors by Structure-Based Virtual Screening Studies and Chemical Optimization"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8842-542X","authenticated-orcid":false,"given":"Doretta","family":"Cuffaro","sequence":"first","affiliation":[{"name":"Department of Pharmacy, University of Pisa, Via Bonanno 6, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7654-6689","authenticated-orcid":false,"given":"Aleix","family":"Gimeno","sequence":"additional","affiliation":[{"name":"Research Group in Cheminformatics & Nutrition, Departament de Bioqu\u00edmica i Biotecnologia, Universitat Rovira i Virgili, Campus de Sescelades, 43007 Tarragona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8094-5965","authenticated-orcid":false,"given":"Bianca Laura","family":"Bernardoni","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Pisa, Via Bonanno 6, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5051-1584","authenticated-orcid":false,"given":"Riccardo","family":"Di Leo","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Pisa, Via Bonanno 6, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2598-8089","authenticated-orcid":false,"given":"Gerard","family":"Pujadas","sequence":"additional","affiliation":[{"name":"Research Group in Cheminformatics & Nutrition, Departament de Bioqu\u00edmica i Biotecnologia, Universitat Rovira i Virgili, Campus de Sescelades, 43007 Tarragona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0348-7497","authenticated-orcid":false,"given":"Santiago","family":"Garcia-Vallv\u00e9","sequence":"additional","affiliation":[{"name":"Research Group in Cheminformatics & Nutrition, Departament de Bioqu\u00edmica i Biotecnologia, Universitat Rovira i Virgili, Campus de Sescelades, 43007 Tarragona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3547-7277","authenticated-orcid":false,"given":"Susanna","family":"Nencetti","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Pisa, Via Bonanno 6, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Armando","family":"Rossello","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Pisa, Via Bonanno 6, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2669-5376","authenticated-orcid":false,"given":"Elisa","family":"Nuti","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Pisa, Via Bonanno 6, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1007\/s11926-005-0006-y","article-title":"Considerations in the Treatment of Early Osteoarthritis","volume":"7","author":"Arabelovic","year":"2005","journal-title":"Curr. 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