{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T08:17:35Z","timestamp":1788337055755,"version":"build-2803163510"},"reference-count":91,"publisher":"American Chemical Society (ACS)","issue":"22","license":[{"start":{"date-parts":[[2015,10,30]],"date-time":"2015-10-30T00:00:00Z","timestamp":1446163200000},"content-version":"vor","delay-in-days":365,"URL":"https:\/\/pubs.acs.org\/page\/policy\/authorchoice_termsofuse.html"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["CA165284"],"award-info":[{"award-number":["CA165284"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000780","name":"European Commission","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,11,26]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>We report a series of 4-sulfamoylphenyl-\u03c9-aminoalkyl ethers as carbonic anhydrase (CA, EC 4.2.1.1) inhibitors. The structure\u2013activity relationship was drawn for the inhibition of four physiologically relevant isoforms: hCA I, II, IX, and XII. Many of these compounds were highly effective, low nanomolar inhibitors of all CA isoforms, whereas several isoform-selective were also identified. X-ray crystal structures of two new sulfonamides bound to the physiologically dominant CA II isoform showed the tails of these derivatives bound within the hydrophobic half of the enzyme active site through van der Waals contacts with Val135, Leu198, Leu204, Trp209, Pro201, and Pro202 amino acids. One of the highly water-soluble compound (as trifluoroacetate salt) showed effective IOP lowering properties in an animal model of glaucoma. Several fluorescent sulfonamides incorporating either the fluorescein-thiourea (7a\u2013c) or tetramethylrhodamine-thiourea (9a,b) moieties were also obtained and showed interesting CA inhibitory properties for the tumor-associated isoforms CA IX and XII.<\/jats:p>","DOI":"10.1021\/jm501497m","type":"journal-article","created":{"date-parts":[[2014,10,30]],"date-time":"2014-10-30T12:38:00Z","timestamp":1414672680000},"page":"9673-9686","source":"Crossref","is-referenced-by-count":49,"title":["A Class of 4-Sulfamoylphenyl-\u03c9-aminoalkyl Ethers with Effective Carbonic Anhydrase Inhibitory Action and Antiglaucoma Effects"],"prefix":"10.1021","volume":"57","author":[{"given":"Murat","family":"Bozdag","sequence":"first","affiliation":[{"name":"Universita\u0300 degli Studi di Firenze , Rm 188, , Via della Lastruccia 3 , ,","place":["Sesto Fiorentino, Florence, Italy, 50019"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Pinard","sequence":"additional","affiliation":[{"name":"University of Florida , , Box 100245, , ,","place":["Gainesville, Florida, United States, 32610"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrizio","family":"Carta","sequence":"additional","affiliation":[{"name":"Universita\u0300 degli Studi di Firenze , Rm 188, , Via della Lastruccia 3 , ,","place":["Sesto Fiorentino, Florence, Italy, 50019"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuela","family":"Masini","sequence":"additional","affiliation":[{"name":"Universita\u0300 degli Studi di Firenze , , Viale Pieraccini 6 , ,","place":["Florence, Italy, 50139"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Scozzafava","sequence":"additional","affiliation":[{"name":"Universita\u0300 degli Studi di Firenze , Rm 188, , Via della Lastruccia 3 , ,","place":["Sesto Fiorentino, Florence, Italy, 50019"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"McKenna","sequence":"additional","affiliation":[{"name":"University of Florida , , Box 100245, , ,","place":["Gainesville, Florida, United States, 32610"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudiu T.","family":"Supuran","sequence":"additional","affiliation":[{"name":"Universita\u0300 degli Studi di Firenze , Rm 188, , Via della Lastruccia 3 , ,","place":["Sesto Fiorentino, Florence, Italy, 50019"]},{"name":"Universita\u0300 degli Studi di Firenze , , Via Ugo Schiff 6 , ,","place":["Sesto Fiorentino, Florence, Italy, 50019"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2014,10,30]]},"reference":[{"key":"2026090203414702700_cit1a","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1021\/cr050262p","article-title":"Carbonic\nanhydrase as a model for biophysical and physical-organic studies\nof proteins and protein-ligand binding","volume":"108","author":"Krishnamurthy","year":"2008","journal-title":"Chem.\nRev."},{"key":"2026090203414702700_cit1b","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1038\/nature10464","article-title":"Evolution of a new enzyme for carbon\ndisulphide conversion by an acidothermophilic archaeon","volume":"478","author":"Smeulders","year":"2011","journal-title":"Nature"},{"key":"2026090203414702700_cit1c","doi-asserted-by":"crossref","first-page":"4421","DOI":"10.1021\/cr200176r","article-title":"Multiple binding\nmodes of inhibitors to carbonic anhydrases: How to design specific\ndrugs targeting 15 different isoforms?","volume":"112","author":"Alterio","year":"2012","journal-title":"Chem.\nRev."},{"key":"2026090203414702700_cit1d","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1038\/nrd2467","article-title":"Carbonic anhydrases: Novel therapeutic\napplications for inhibitors and activators","volume":"7","author":"Supuran","year":"2008","journal-title":"Nat. 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Chem."},{"key":"2026090203414702700_cit8b","doi-asserted-by":"crossref","first-page":"388","DOI":"10.3109\/14756366.2011.649268","article-title":"Inhibition of the \u03b1- and \u03b2-carbonic anhydrases\nfrom the gastric pathogen Helycobacter pylori with anions","volume":"28","author":"Maresca","year":"2013","journal-title":"J. Enzyme Inhib. Med. Chem."},{"key":"2026090203414702700_cit9","doi-asserted-by":"crossref","first-page":"4389","DOI":"10.1016\/j.bmcl.2014.08.015","article-title":"Discovery of a new\nfamily of carbonic anhydrases in the malaria pathogen Plasmodium falciparum \u2013 the \u03b7-carbonic\nanhydrases","volume":"24","author":"Del Prete","year":"2014","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"2026090203414702700_cit10a","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1046\/j.1365-201X.2002.01010.x","article-title":"Localization of\na protein inhibitor of carbonic anhydrase\nin pig tissues","volume":"176","author":"Ridderstra\u030ale","year":"2002","journal-title":"Acta Physiol. Scand."},{"key":"2026090203414702700_cit10b","doi-asserted-by":"crossref","first-page":"5529","DOI":"10.1021\/jm3004587","article-title":"Protein\u2013protein\ninteractions: Inhibition of mammalian carbonic anhydrases I-XV by\nthe murine inhibitor of carbonic anhydrase and other members of the\ntransferrin family","volume":"55","author":"Durdagi","year":"2012","journal-title":"J. Med. Chem."},{"key":"2026090203414702700_cit11a","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1517\/17460441.2013.795145","article-title":"Exploiting\nthe hydrophobic and hydrophilic binding sites for designing carbonic\nanhydrase inhibitors","volume":"8","author":"De Simone","year":"2013","journal-title":"Expert Opin. Drug Discovery"},{"key":"2026090203414702700_cit11b","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1517\/13543776.2013.794788","article-title":"Antiglaucoma carbonic anhydrase inhibitors: A patent\nreview","volume":"23","author":"Masini","year":"2013","journal-title":"Expert Opin. Ther. Pat."},{"key":"2026090203414702700_cit11c","doi-asserted-by":"crossref","first-page":"3467","DOI":"10.1016\/j.bmcl.2010.05.009","article-title":"Carbonic anhydrase inhibitors","volume":"20","author":"Supuran","year":"2010","journal-title":"Bioorg. Med. Chem. 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Pat."},{"key":"2026090203414702700_cit15a","doi-asserted-by":"crossref","first-page":"4231","DOI":"10.1002\/anie.201310709","article-title":"A small-molecule drug\nconjugate for the treatment of carbonic anhydrase IX expressing tumors","volume":"53","author":"Krall","year":"2014","journal-title":"Angew. Chem., Int. Ed."},{"key":"2026090203414702700_cit15b","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1517\/13543776.2013.798648","article-title":"Anticancer carbonic anhydrase inhibitors:\nA patent review (2008\u20132013)","volume":"23","author":"Monti","year":"2013","journal-title":"Expert Opin.\nTher. Pat."},{"key":"2026090203414702700_cit15c","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.ctrv.2012.08.004","article-title":"New strategies\nfor targeting the hypoxic tumour microenvironment in breast cancer","volume":"39","author":"Ward","year":"2013","journal-title":"Cancer Treat. Rev."},{"key":"2026090203414702700_cit15d","doi-asserted-by":"crossref","first-page":"8271","DOI":"10.1021\/jm200983e","article-title":"Glycosyl coumarin\ncarbonic anhydrase IX and XII inhibitors strongly attenuate the growth\nof primary breast tumors","volume":"54","author":"Touisni","year":"2011","journal-title":"J. Med. Chem."},{"key":"2026090203414702700_cit16a","doi-asserted-by":"crossref","first-page":"291","DOI":"10.4155\/9781909453913","article-title":"Carbonic anhydrase\ninhibitors drug design","volume-title":"Carbonic Anhydrase:\nMechanism, regulation, Links to Disease, and Industrial Applications","author":"Supuran","year":"2014"},{"key":"2026090203414702700_cit16b","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1007\/978-94-007-7359-2_15","volume":"75","year":"2014","journal-title":"Subcell. 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Chem."},{"key":"2026090203414702700_cit18d","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1002\/med.20141","article-title":"Therapeutic applications\nof glycosidic carbonic anhydrase inhibitors","volume":"29","author":"Winum","year":"2009","journal-title":"Med. Res. Rev."},{"key":"2026090203414702700_cit18e","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1016\/j.bmcl.2009.01.079","article-title":"Carbonic anhydrase inhibitors: two-prong\nversus mono-prong inhibitors of isoforms I, II, IX, and XII exemplified\nby photochromic cis-1,2-\u03b1-dithienylethene derivatives","volume":"19","author":"Vomasta","year":"2009","journal-title":"Bioorg. Med. Chem. 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