{"abstract": "Inhibition of 13 mammalian isoforms of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1), CA I-XV, with thioxolone (6-hydroxy-1,3-benzoxathiol-2-one) and two sulfonamides was investigated. Thioxolone was inefficient for generating isozyme-selective inhibitors, since except for CA I which is inhibited in the nanomolar range (K(I) of 91 nM), the remaining 12 isoforms were inhibited with a very flat profile (K(I)s in the range of only 4.93-9.04 microM). In contrast to thioxolone, 3,5-dichloro-4-hydroxybenzenesulfonamide as well as the clinically used heterocyclic sulfonamide acetazolamide showed K(I)s in the range of 58 nM-78.6 microM and 2.5 nM-200 microM, respectively, against the 13 investigated mammalian CAs. The sulfonamide zinc-binding group is thus superior to the thiol one for generating CA inhibitors with a varied and sometimes isozyme-selective inhibition profile against the mammalian enzymes.", "authors": "Innocenti A, Maresca A, Scozzafava A, Supuran CT.", "chembl_release": {"chembl_release": "CHEMBL_2", "creation_date": "2009-11-30"}, "contact": null, "doc_type": "PUBLICATION", "document_chembl_id": "CHEMBL1155067", "doi": "10.1016/j.bmcl.2008.06.024", "doi_chembl": null, "first_page": "3938", "issue": "14", "journal": "Bioorg Med Chem Lett", "journal_full_title": "Bioorganic & medicinal chemistry letters.", "last_page": "3941", "patent_id": null, "pubmed_id": 18572406, "src_id": 1, "title": "Carbonic anhydrase inhibitors: thioxolone versus sulfonamides for obtaining isozyme-selective inhibitors?", "volume": "18", "year": 2008}