{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T02:52:14Z","timestamp":1792119134623,"version":"4.4.0"},"reference-count":63,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T00:00:00Z","timestamp":1764892800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009687","name":"Wroclaw Medical University","doi-asserted-by":"publisher","award":["SUBK.D070.24.017"],"award-info":[{"award-number":["SUBK.D070.24.017"]}],"id":[{"id":"10.13039\/501100009687","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009687","name":"Wroclaw Medical University","doi-asserted-by":"publisher","award":["SUBZ.D290.25.066"],"award-info":[{"award-number":["SUBZ.D290.25.066"]}],"id":[{"id":"10.13039\/501100009687","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>A series of dimethylpyridine-3-carboxamide derivatives was designed as potential, selective, non-zinc chelating inhibitors of matrix metalloproteinase 13 (MMP-13), and subsequently synthesized. The identity of the obtained compounds was confirmed by FT-IR, 1H\/13C NMR, and HR-MS methods. Fluorescence spectroscopy was applied to study the interaction of synthesized compounds with human serum albumin, providing insight into their potential transport properties in plasma. In parallel, the electronic properties and reactivity parameters relevant to enzyme binding of the designed molecules were analyzed using density functional theory. Molecular docking and molecular dynamics simulations revealed the compounds to interact preferentially and stably within the S1 pocket of MMP-13 via hydrogen bonds and \u03c0-stacking interactions. The calculated binding free energy confirmed the stability and persistence of the complexes during simulation, indicating a strong and specific recognition pattern. On the other hand, their affinity towards MMP-8 was considerably weaker, which is consistent with the predicted selectivity profile. In addition, the biological evaluation confirmed MMP-13 inhibition. Finally, in vitro tests revealed their cytotoxic activity against cancer cell lines.<\/jats:p>","DOI":"10.3390\/molecules30244662","type":"journal-article","created":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T13:17:07Z","timestamp":1764940627000},"page":"4662","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["New Dimethylpyridine-3-Carboxamide Derivatives as MMP-13 Inhibitors with Anticancer Activity"],"prefix":"10.3390","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-7207-1508","authenticated-orcid":false,"given":"Remigiusz","family":"P\u0142aczek","sequence":"first","affiliation":[{"name":"Department of Basic Chemical Sciences, Faculty of Pharmacy, Wroclaw Medical University, Borowska 211, 50-556 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1939-5500","authenticated-orcid":false,"given":"Tomasz","family":"Janek","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Food Microbiology, Faculty of Biotechnology and Food Science, Wroclaw University of Environmental and Life Sciences, Che\u0142mo\u0144skiego 37, 51-630 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5689-4889","authenticated-orcid":false,"given":"Ma\u0142gorzata","family":"Strzelecka","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, Faculty of Pharmacy, Wroclaw Medical University, Borowska 211, 50-556 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0730-8975","authenticated-orcid":false,"given":"Aleksandra","family":"Kotynia","sequence":"additional","affiliation":[{"name":"Department of Basic Chemical Sciences, Faculty of Pharmacy, Wroclaw Medical University, Borowska 211, 50-556 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4613-025X","authenticated-orcid":false,"given":"Piotr","family":"\u015awi\u0105tek","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, Faculty of Pharmacy, Wroclaw Medical University, Borowska 211, 50-556 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5758-9667","authenticated-orcid":false,"given":"\u017baneta","family":"Czy\u017cnikowska","sequence":"additional","affiliation":[{"name":"Department of Basic Chemical Sciences, Faculty of Pharmacy, Wroclaw Medical University, Borowska 211, 50-556 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1038\/s41584-023-00966-w","article-title":"Matrix Metalloproteinases in Arthritis: Towards Precision Medicine","volume":"19","author":"Grillet","year":"2023","journal-title":"Nat. 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