| Title | Carbonic anhydrase inhibitors: Thioxolone versus sulfonamides for obtaining isozyme-selective inhibitors? | | Author(s) | Innocenti A, Maresca A, Scozzafava A, Supuran CT | | Institution | Università degli Studi di Firenze, Polo Scientifico, Laboratorio di Chimica Bioinorganica, Room 188, Via della Lastruccia 3, 50019 Sesto Fiorentino (Florence), Italy. | | Source | Bioorg Med Chem Lett 2008 Jun 12. | | 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 91nM), the remaining 12 isoforms were inhibited with a very flat profile (K(I)s in the range of only 4.93-9.04muM). 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 58nM-78.6muM and 2.5nM-200muM, 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. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 18572406 |
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