{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:38:12Z","timestamp":1786977492015,"version":"build-2736575974"},"reference-count":71,"publisher":"Wiley","issue":"13","license":[{"start":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T00:00:00Z","timestamp":1783296000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T00:00:00Z","timestamp":1783296000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemMedChem"],"published-print":{"date-parts":[[2026,7,14]]},"abstract":"<jats:p>\n                    A novel library of diazo and pyrazole\u2010carboxamide\u2010linked molecules containing the sulfonamide pharmacophore was developed and synthesized, yielding selective inhibitors of clinically relevant carbonic anhydrase (CA) isoforms. The synthesis method involved the production of diazonium salts from 4\u2010 and 3\u2010aminobenzenesulfonamide precursors, followed by cyclization and further functionalization to yield structurally diverse pyrazole derivatives. All compounds were evaluated for their inhibitory efficacy against hCA I and II (cytosolic isoforms) and the tumor\u2010associated isoenzymes hCA IX and XII; also, cytotoxicity and molecular modeling studies were conducted for the compounds. The newly synthesized hybrid compounds displayed extensive inhibitory activity, with most derivatives showing significant potency and selectivity for cancer\u2010associated isoforms. More specifically, para\u2010substituted analogs exhibited enhanced inhibitory properties relative to their meta\u2010substituted counterparts. Compound\n                    <jats:bold>5f<\/jats:bold>\n                    , with a 3,4\u2010dichloro motif, exhibited the highest activity with a very low K\n                    <jats:sub>I<\/jats:sub>\n                    value of 1.8\u2009nM against hCA IX, greatly surpassing the reference drug acetazolamide. Electron\u2010withdrawing substituents improved inhibitory efficacy, whereas electron\u2010donating groups often reduced activity. Furthermore, compounds\n                    <jats:bold>5f<\/jats:bold>\n                    (A549: 41.17\u2009\u03bcM; HCT116: 4.47\u2009\u03bcM) and\n                    <jats:bold>6c<\/jats:bold>\n                    (A549: 14.64\u2009\u03bcM; HCT116: 4.03\u2009\u03bcM) showed the lowest IC\n                    <jats:sub>50<\/jats:sub>\n                    values in both cell lines. The findings emphasize diazo\u2010 and pyrazole\u2010carboxamide\u2010linked benzenesulfonamides as promising scaffolds for advancing isoform\u2010selective carbonic anhydrase inhibitors.\n                  <\/jats:p>","DOI":"10.1002\/cmdc.70369","type":"journal-article","created":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T04:29:41Z","timestamp":1783398581000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Investigating the Inhibitory Properties of Diazo and Pyrazole\u2010Carboxamide\u2010Linked Benzenesulfonamides Against Carbonic Anhydrase Isoforms I, II, IX, and XII"],"prefix":"10.1002","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4506-5265","authenticated-orcid":false,"given":"Suleyman","family":"Akocak","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Chemistry Faculty of Pharmacy Ad\u0131yaman University  Ad\u0131yaman 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