{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,8]],"date-time":"2026-02-08T04:15:29Z","timestamp":1770524129849,"version":"3.49.0"},"reference-count":31,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2020,4,9]],"date-time":"2020-04-09T00:00:00Z","timestamp":1586390400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>A series of new 3-phenyl-5-aryl-N-(4-sulfamoylphenyl)-4,5-dihydro-1H-pyrazole-1-carboxamide derivatives was designed here, synthesized, and studied for carbonic anhydrase (CAs, EC 4.2.1.1) inhibitory activity against the human (h) isozymes I, II, and VII (cytosolic, off-target isoforms), and IX and XII (anticancer drug targets). Generally, CA I was not effectively inhibited, whereas effective inhibitors were identified against both CAs II (KIs in the range of 5.2\u2013233 nM) and VII (KIs in the range of 2.3\u2013350 nM). Nonetheless, CAs IX and XII were the most susceptible isoforms to this class of inhibitors. In particular, compounds bearing an unsubstituted phenyl ring at the pyrazoline 3 position showed 1.3\u20131.5 nM KIs against CA IX. In contrast, a subset of derivatives having a 4-halo-phenyl at the same position of the aromatic scaffold even reached subnanomolar KIs against CA XII (0.62\u20130.99 nM). Docking studies with CA IX and XII were used to shed light on the derivative binding mode driving the preferential inhibition of the tumor-associated CAs. The identified potent and selective CA IX\/XII inhibitors are of interest as leads for the development of new anticancer strategies.<\/jats:p>","DOI":"10.3390\/ijms21072621","type":"journal-article","created":{"date-parts":[[2020,4,9]],"date-time":"2020-04-09T14:42:03Z","timestamp":1586443323000},"page":"2621","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Aryl-4,5-dihydro-1H-pyrazole-1-carboxamide Derivatives Bearing a Sulfonamide Moiety Show Single-digit Nanomolar-to-Subnanomolar Inhibition Constants against the Tumor-associated Human Carbonic Anhydrases IX and XII"],"prefix":"10.3390","volume":"21","author":[{"given":"Priya","family":"Hargunani","sequence":"first","affiliation":[{"name":"Bharati Vidyapeeth\u2019s College of Pharmacy, Navi Mumbai 400 614, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nikhil","family":"Tadge","sequence":"additional","affiliation":[{"name":"Bharati Vidyapeeth\u2019s College of Pharmacy, Navi Mumbai 400 614, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariangela","family":"Ceruso","sequence":"additional","affiliation":[{"name":"Neurofarba Dept., Section of Pharmaceutical and Nutraceutical Sciences, Universit\u00e1 degli Studi di Firenze, Via U. Schiff 6, Sesto Fiorentino, 50019 Florence, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janis","family":"Leitans","sequence":"additional","affiliation":[{"name":"Latvian Biomedical Research and Study Center, Ratsupites 1, LV-1067 Riga, Latvia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andris","family":"Kazaks","sequence":"additional","affiliation":[{"name":"Latvian Biomedical Research and Study Center, Ratsupites 1, LV-1067 Riga, Latvia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaspars","family":"Tars","sequence":"additional","affiliation":[{"name":"Latvian Biomedical Research and Study Center, Ratsupites 1, LV-1067 Riga, Latvia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paola","family":"Gratteri","sequence":"additional","affiliation":[{"name":"Neurofarba Dept., Section of Pharmaceutical and Nutraceutical Sciences, Universit\u00e1 degli Studi di Firenze, Via U. Schiff 6, Sesto Fiorentino, 50019 Florence, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4262-0323","authenticated-orcid":false,"given":"Claudiu T.","family":"Supuran","sequence":"additional","affiliation":[{"name":"Neurofarba Dept., Section of Pharmaceutical and Nutraceutical Sciences, Universit\u00e1 degli Studi di Firenze, Via U. Schiff 6, Sesto Fiorentino, 50019 Florence, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3342-702X","authenticated-orcid":false,"given":"Alessio","family":"Nocentini","sequence":"additional","affiliation":[{"name":"Neurofarba Dept., Section of Pharmaceutical and Nutraceutical Sciences, Universit\u00e1 degli Studi di Firenze, Via U. Schiff 6, Sesto Fiorentino, 50019 Florence, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mrunmayee P.","family":"Toraskar","sequence":"additional","affiliation":[{"name":"Bharati Vidyapeeth\u2019s College of Pharmacy, Navi Mumbai 400 614, India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,4,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"15184","DOI":"10.1073\/pnas.96.26.15184","article-title":"Carbonic anhydrase is an ancient enzyme widespread in prokaryotes","volume":"96","author":"Smith","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1038\/nrd2467","article-title":"Carbonic anhydrases: Novel therapeutic applications for inhibitors and activators","volume":"7","author":"Supuran","year":"2008","journal-title":"Nat. Rev. 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