{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T12:41:04Z","timestamp":1788612064567,"version":"build-2803163510"},"reference-count":42,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,4,17]],"date-time":"2025-04-17T00:00:00Z","timestamp":1744848000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Medical University of Gda\u0144sk under the program on Maintaining and Developing Research Potential\u2014ST","award":["01-50024\/0006140\/01\/509\/509\/0\/2024"],"award-info":[{"award-number":["01-50024\/0006140\/01\/509\/509\/0\/2024"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>In the search for new selective inhibitors of human carbonic anhydrase (hCA), particularly the cancer-associated isoforms hCA IX and hCA XII, a series of 4-substituted pyridine-3-sulfonamides was synthesized using the \u201cclick\u201d CuAAC reaction, proven by X-ray crystallography, and evaluated for their inhibitory activity against hCA I, hCA II, hCA IX, and hCA XII. Additional molecular docking studies and cytostatic activity assays on three cancer cell lines were conducted. The compounds exhibited a broad range of inhibitory activity, with KI reaching 271 nM for hCA II, 137 nM for hCA IX, and 91 nM for hCA XII. Notably, compound 4 demonstrated up to 5.9-fold selectivity toward the cancer-associated hCA IX over the ubiquitous hCA II, while compound 6 exhibited a remarkable 23.3-fold selectivity between transmembrane isoforms hCA IX and hCA XII. Molecular docking studies have shown the possibility of selective interaction with the hydrophilic or lipophilic half of the active site, what results from the adjacent (3,4) position of the \u201ctail\u201d in relation to the sulfonamide group.<\/jats:p>","DOI":"10.3390\/ijms26083817","type":"journal-article","created":{"date-parts":[[2025,4,17]],"date-time":"2025-04-17T20:50:46Z","timestamp":1744923046000},"page":"3817","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["4-Substituted Pyridine-3-Sulfonamides as Carbonic Anhydrase Inhibitors Modified by Click Tailing: Synthesis, Activity, and Docking Studies"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8347-9659","authenticated-orcid":false,"given":"Krzysztof","family":"Szafra\u0144ski","sequence":"first","affiliation":[{"name":"Department of Organic Chemistry, Medical University of Gda\u0144sk, Al. Gen. J. Hallera 107, 80-416 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2794-5031","authenticated-orcid":false,"given":"Jaros\u0142aw","family":"S\u0142awi\u0144ski","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry, Medical University of Gda\u0144sk, Al. Gen. J. Hallera 107, 80-416 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8105-2555","authenticated-orcid":false,"given":"Anna","family":"Kawiak","sequence":"additional","affiliation":[{"name":"Intercollegiate Faculty of Biotechnology, University of Gda\u0144sk, Abrahama 58, 80-307 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2453-8214","authenticated-orcid":false,"given":"Jaros\u0142aw","family":"Chojnacki","sequence":"additional","affiliation":[{"name":"Department of Inorganic Chemistry, Faculty of Chemistry, Gda\u0144sk University of Technology, G. Narutowicza 11\/12, 80-233 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0116-3728","authenticated-orcid":false,"given":"Micha\u0142","family":"Kosno","sequence":"additional","affiliation":[{"name":"2nd Department of Radiology, Medical University of Gda\u0144sk, Mariana Smoluchowskiego 17, 80-210 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7364-1499","authenticated-orcid":false,"given":"Andrea","family":"Ammara","sequence":"additional","affiliation":[{"name":"Section of Pharmaceutical and Nutraceutical Sciences, Department of NEUROFARBA, University of Florence, Polo Scientifico, Via U. 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