title: Carbonic anhydrase inhibitors. Inhibition of red blood cell ostrich (Struthio camelus) carbonic anhydrase with a series of aromatic and heterocyclic sulfonamides.
abstract: The purification of red blood cell carbonic anhydrase (CA, EC 4.2.1.1) from ostrich (scCA) blood is reported, as well as an inhibition study of this enzyme with a series of aromatic and heterocylic sulfonamides. The ostrich enzyme showed a high activity, comparable to that of the human isozyme II, with kcat, of 1.2 x 10(6) s(-1) and kcat/KM of 1.8 x 10(7) M(-1)s(-1), and an inhibition profile quite different from that of the human red blood cell cytosolic isozymes hCA I and II. scCA has generally a lower affinity for sulfonamide inhibitors as compared to hCA I and II. The only sulfonamide which behaved as a very potent inhibitor of this enzyme was ethoxzolamide (KI = 3.9 nM) whereas acetazolamide and sulfanilamide behaved as weaker inhibitors (inhibition constants in the range 303-570 nM). Several other aromatic and heterocyclic sulfonamides, mostly derivatives of sulfanilamide, homosulfanilamide, 4-aminoethylbenzenesulfonamide or 5-amino-1,3,4-thiadiazole-2-sulfonamide, showed good affinities for the ostrich enzyme, with KI values in the range 25-72 nM.
authors.affiliation: Polo Scientifico, Laboratorio di Chimica Bioinorganica, Universitá degli Studi di Firenze, Sesto Fiorentino, Florence, Italy.
authors.forename: Ozen
authors.initials: O
authors.lastname: Ozensoy
authors.forename: Semra
authors.initials: S
authors.lastname: Isik
authors.forename: Oktay
authors.initials: O
authors.lastname: Arslan
authors.forename: Mikail
authors.initials: M
authors.lastname: Arslan
authors.forename: Andrea
authors.initials: A
authors.lastname: Scozzafava
authors.forename: Claudiu T
authors.initials: CT
authors.lastname: Supuran
mesh_terms: D000818:Animals; D024401:Carbonic Anhydrase I / Q000037:antagonists & inhibitors*; D024402:Carbonic Anhydrase II / Q000037:antagonists & inhibitors*; D002257:Carbonic Anhydrase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D004912:Erythrocytes / Q000201:enzymology*; D005260:Female; D013329:Structure-Activity Relationship; D020310:Struthioniformes / Q000378:metabolism*; D013449:Sulfonamides / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D013449:Sulfonamides; D024401:Carbonic Anhydrase I; D024402:Carbonic Anhydrase II