{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T00:08:00Z","timestamp":1782950880350,"version":"3.54.5"},"reference-count":34,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2023,11,26]],"date-time":"2023-11-26T00:00:00Z","timestamp":1700956800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Elettra and BeamLine","award":["20220596"],"award-info":[{"award-number":["20220596"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Sulfonamides remain an important class of drugs, especially because of their inhibitory effects on carbonic anhydrases. Herein, we have synthesized several sulfonamides and tested them for their inhibitory activity against carbonic anhydrases hCA I, hCA II, hCA IX, and hCA XII, respectively. Thereby, biphenyl- and benzylphenyl-substituted sulfonamides showed high selectivity against hCA IX and hCA XII; these enzymes are common targets in the treatment of hypoxic cancers, and noteworthy inhibitory activity was observed for several compounds toward hCA I that might be of interest for future applications to treat cerebral edema. Compound 3 (4-[3-(2-benzylphenyl)ureido]benzenesulfonamide) held an exceptionally low Ki value of 1.0 nM for hCA XII.<\/jats:p>","DOI":"10.3390\/molecules28237782","type":"journal-article","created":{"date-parts":[[2023,11,27]],"date-time":"2023-11-27T03:48:17Z","timestamp":1701056897000},"page":"7782","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Ureidobenzenesulfonamides as Selective Carbonic Anhydrase I, IX, and XII Inhibitors"],"prefix":"10.3390","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0191-5651","authenticated-orcid":false,"given":"Toni C.","family":"Denner","sequence":"first","affiliation":[{"name":"Organic Chemistry, Martin-Luther University Halle-Wittenberg, Kurt-Mothes, Str. 2, D-06120 Halle (Saale), Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1470-7192","authenticated-orcid":false,"given":"Andrea","family":"Angeli","sequence":"additional","affiliation":[{"name":"Section of Pharmaceutical Sciences, Neurofarba Department, University of Florence, Via Ugo Schiff 6, Sesto Florentino, 50019 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Ferraroni","sequence":"additional","affiliation":[{"name":"Department of Chemistry \u201cUgo Schiff\u201d, University of Florence, Via della Lastruccia 3-13, Sesto Fiorentino, 50019 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4262-0323","authenticated-orcid":false,"given":"Claudiu T.","family":"Supuran","sequence":"additional","affiliation":[{"name":"Section of Pharmaceutical Sciences, Neurofarba Department, University of Florence, Via Ugo Schiff 6, Sesto Florentino, 50019 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7911-290X","authenticated-orcid":false,"given":"Ren\u00e9","family":"Csuk","sequence":"additional","affiliation":[{"name":"Organic Chemistry, Martin-Luther University Halle-Wittenberg, Kurt-Mothes, Str. 2, D-06120 Halle (Saale), Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1002\/prac.19080770129","article-title":"Sulphamides of p-Aminobenzenesulphonic Acid","volume":"77","author":"Gelmo","year":"1908","journal-title":"Vienna. J. Prakt Chem."},{"key":"ref_2","first-page":"15","article-title":"The chemotherapy of bacterial infections","volume":"71A","author":"Mietzsch","year":"1938","journal-title":"Ber. Dtsch. Chem. Ges. A"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1055\/s-0028-1129486","article-title":"Chemotherapy of bacterial infections","volume":"61","author":"Domagk","year":"1935","journal-title":"Dtsch. Med. Wochenschr."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1038\/146164a0","article-title":"Sulfanilamide as a specific inhibitor of carbonic anhydrase","volume":"146","author":"Mann","year":"1940","journal-title":"Nature"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"10837","DOI":"10.1021\/bi980046t","article-title":"The catalytic properties of murine carbonic anhydrase VII","volume":"37","author":"Earnhardt","year":"1998","journal-title":"Biochemistry"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/S1359-6349(10)71132-0","article-title":"Tumour metabolic adaptation to hypoxic and acidic stress","volume":"8","author":"Chiche","year":"2010","journal-title":"Ejc Suppl."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1016\/j.semcancer.2008.03.011","article-title":"Adaptation to hypoxia and acidosis in carcinogenesis and tumor progression","volume":"18","author":"Fang","year":"2008","journal-title":"Semin. Cancer Biol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Verduzco, D., Lloyd, M., Xu, L.P., Ibrahim-Hashim, A., Balagurunathan, Y., Gatenby, R.A., and Gillies, R.J. (2015). Intermittent Hypoxia Selects for Genotypes and Phenotypes That Increase Survival, Invasion, and Therapy Resistance. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0120958"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2569","DOI":"10.1016\/j.bmc.2017.03.027","article-title":"Synthesis and carbonic anhydrase inhibition of a series of SLC-011.1 analogs","volume":"25","author":"Carta","year":"2017","journal-title":"Bioorgan. Med. Chem."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Singh, S., Lomelino, C.L., Mboge, M.Y., Frost, S.C., and McKenna, R. (2018). Cancer Drug Development of Carbonic Anhydrase Inhibitors beyond the Active Site. Molecules, 23.","DOI":"10.3390\/molecules23051045"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1080\/14756366.2018.1532419","article-title":"The carbonic anhydrase IX inhibitor SLC-0111 sensitises cancer cells to conventional chemotherapy","volume":"34","author":"Andreucci","year":"2019","journal-title":"J. Enzym. Inhib. Med. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/j.ejmech.2016.01.030","article-title":"Amido\/ureidosubstituted benzenesulfonamides-isatin conjugates as low nanomolar\/subnanomolar inhibitors of the tumor-associated carbonic anhydrase isoform XII","volume":"110","author":"Eldehna","year":"2016","journal-title":"Eur. J. Med. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1016\/j.bioorg.2018.01.021","article-title":"New anticancer drug canditates sulfonamides as selective hCA IX or hCA XII inhibitors","volume":"77","author":"Gul","year":"2018","journal-title":"Bioorg. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/j.ejmech.2017.03.026","article-title":"Structure activity study of carbonic anhydrase IX: Selective inhibition with ureido-substituted benzenesulfonamides","volume":"132","author":"Mboge","year":"2017","journal-title":"Eur. J. Med. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.ejmech.2018.05.034","article-title":"Synthesis, characterization and biological evaluation of tertiary sulfonamide derivatives of pyridyl-indole based heteroaryl chalcone as potential carbonic anhydrase IX inhibitors and anticancer agents","volume":"155","author":"Peerzada","year":"2018","journal-title":"Eur. J. Med. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1080\/13543784.2018.1548608","article-title":"Carbonic anhydrase inhibitors as emerging agents for the treatment and imaging of hypoxic tumors","volume":"27","author":"Supuran","year":"2018","journal-title":"Expert Opin. Investig. Drugs"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1002\/med.20112","article-title":"Carbonic anhydrase IX: A new druggable target for the design of antitumor agents","volume":"28","author":"Winum","year":"2008","journal-title":"Med. Res. Rev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1097\/COC.0000000000000691","article-title":"A Phase 1 Study of SLC-0111, a Novel Inhibitor of Carbonic Anhydrase IX, in Patients With Advanced Solid Tumors","volume":"43","author":"McDonald","year":"2020","journal-title":"Am. J. Clin. Oncol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.1080\/13543784.2021.2014813","article-title":"Carbonic anhydrase inhibitors: An update on experimental agents for the treatment and imaging of hypoxic tumors","volume":"30","author":"Supuran","year":"2021","journal-title":"Expert. Opin. Investig. Drug"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"5","DOI":"10.4155\/fmc-2022-0249","article-title":"Latest advances in specific inhibition of tumor-associated carbonic anhydrases","volume":"15","author":"Supuran","year":"2023","journal-title":"Future Med. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Serbian, I., Schwarzenberger, P., Loesche, A., Hoenke, S., Al-Harrasi, A., and Csuk, R. (2019). Ureidobenzenesulfonamides as efficient inhibitors of carbonic anhydrase II. Bioorg. Chem., 91.","DOI":"10.1016\/j.bioorg.2019.103123"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2081","DOI":"10.1016\/j.ophtha.2014.05.013","article-title":"Global Prevalence of Glaucoma and Projections of Glaucoma Burden through 2040: A Systematic Review and Meta-Analysis","volume":"121","author":"Tham","year":"2014","journal-title":"Ophthalmology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1056\/NEJMoa2212948","article-title":"Lecanemab in Early Alzheimers Disease","volume":"388","author":"Swanson","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1080\/13543784.2021.1948010","article-title":"Still grasping at straws: Donanemab in Alzheimer\u2019s disease. Expert Opin","volume":"30","author":"Doggrell","year":"2021","journal-title":"Invest Drugs"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1691","DOI":"10.1056\/NEJMoa2100708","article-title":"Donanemab in early Alzheimer\u2019s disease","volume":"384","author":"Mintun","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1007\/s12028-021-01261-w","article-title":"Acetazolamide Alleviate Cerebral Edema Induced by Ischemic Stroke Through Inhibiting the Expression of AQP4 mRNA","volume":"36","author":"Hao","year":"2022","journal-title":"Neurocrit. Care"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1517\/14656566.9.1.119","article-title":"High hopes at high altitudes: Pharmacotherapy for acute mountain sickness and high-altitude cerebral and pulmonary oedema","volume":"9","author":"Wright","year":"2008","journal-title":"Expert Opin. Pharmacother."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1021\/acs.jmedchem.1c01906","article-title":"One-Pot Procedure for the Synthesis of Asymmetric Substituted Ureido Benzene Sulfonamides as Effective Inhibitors of Carbonic Anhydrase Enzymes","volume":"65","author":"Vannozzi","year":"2022","journal-title":"J. Med. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Supuran, C.T. (2023). A simple yet multifaceted 90 years old, evergreen enzyme: Carbonic anhydrase, its inhibition and activation. Bioorg. Med. Chem. Lett., 93.","DOI":"10.1016\/j.bmcl.2023.129411"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1007\/978-1-4020-6316-9_4","article-title":"Procesing diffraction data with mosflm","volume":"Volume 245","author":"Read","year":"2007","journal-title":"Evolving Methods for Macromolecular Crystallography"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1107\/S0907444996012255","article-title":"Refinement of macromolecular structures by the maximum-likelihood method","volume":"53","author":"Murshudov","year":"1997","journal-title":"Acta Crystallogr. D Biol. Crystallogr."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1107\/S0907444910007493","article-title":"Features and development of Coot","volume":"66","author":"Emsley","year":"2010","journal-title":"Acta Crystallogr. D Biol. Crystallogr."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1002\/prot.10286","article-title":"Structure validation by C\u03b1 geometry: \u03d5,\u03c8 and C\u03b2 deviation","volume":"50","author":"Lovell","year":"2003","journal-title":"Proteins"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1002\/jcc.20084","article-title":"UCSF Chimera\u2014A visualization system for exploratory research and analysis","volume":"25","author":"Pettersen","year":"2004","journal-title":"J. Comput. Chem."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/23\/7782\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:30:31Z","timestamp":1760131831000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/23\/7782"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,26]]},"references-count":34,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["molecules28237782"],"URL":"https:\/\/doi.org\/10.3390\/molecules28237782","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,26]]}}}