title: Carbonic anhydrase inhibitors: inhibition of human and bovine isoenzymes by benzenesulphonamides, cyclitols and phenolic compounds.
abstract: Carbonic anhydrase inhibitors (CAIs) are a class of pharmaceuticals used as anti-glaucoma agents, diuretics and anti-epileptics. We report here the inhibitory capacities of benzenesulphonamides, cyclitols and phenolic compounds 1-11 against three human CA isozymes (hCA I, hCA II and hCA VI) and bovine skeletal muscle carbonic anhydrase III (bCA III). The four isozymes showed quite diverse inhibition profiles with K(i) values ranging from low micromolar to millimolar concentrations against all isoenzymes. Compound 5 and 6 had more powerful inhibitory action against hCA I and very similar action against hCA II and hCA VI as compared with acetazolamide (AZA) and sulphapyridine (SPD), specific CAIs. Probably the inhibition mechanism of the tested compounds is distinct of the sulphonamides with RSO(2)NH(2) groups and similar to that of the coumarins/lacosamide, i.e. binding to a distinct part of the active site than that where sulphonamides bind. These data may lead to drug design campaigns of effective CAIs possessing a diverse inhibition mechanism compared to other sulphonamide/sulphamate inhibitors.
authors: Ondokuz Mayis University, Agricultural Faculty, Department of Agricultural Biotechnology, Samsun, Turkey.
authors: Deniz
authors: D
authors: Ekinci
authors: Namudar I
authors: NI
authors: Kurbanoglu
authors: Emine
authors: E
authors: Salamci
authors: Murat
authors: M
authors: Şentürk
authors: Claudiu T
authors: CT
authors: Supuran
mesh_terms: D000818:Animals; D001557:Benzenesulfonates / Q000138:chemical synthesis* / Q000737:chemistry; D002256:Carbonic Anhydrases / Q000737:chemistry* / Q000302:isolation & purification; D002417:Cattle; D054812:Cyclitols / Q000138:chemical synthesis* / Q000737:chemistry; D004591:Electrophoresis, Polyacrylamide Gel; D057075:Enzyme Assays; D004912:Erythrocytes / Q000737:chemistry / Q000201:enzymology; D006801:Humans; D007527:Isoenzymes / Q000737:chemistry / Q000302:isolation & purification; D007700:Kinetics; D015394:Molecular Structure; D018482:Muscle, Skeletal / Q000737:chemistry / Q000201:enzymology; D010636:Phenols / Q000138:chemical synthesis* / Q000737:chemistry; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D001557:Benzenesulfonates; D054812:Cyclitols; D007527:Isoenzymes; D010636:Phenols; D013449:Sulfonamides; D002256:Carbonic Anhydrases