title: Carbonic anhydrase inhibitors. Inhibition of human erythrocyte isozymes I and II with a series of antioxidant phenols.
abstract: The inhibition of two human cytosolic carbonic anhydrase (hCA, EC 4.2.1.1) isozymes I and II, with a series of phenol derivatives was investigated by using the esterase assay, with 4-nitrophenyl acetate as substrate. 2,6-Dimethylphenol, 2,6-diisopropylphenol (propofol), 2,6-di-t-butylphenol, butylated hydroxytoluene, butylated hydroxyanisole, vanillin, guaiacol, di(2,6-dimethylphenol), di(2,6-diisopropylphenol), di(2,6-di-t-butylphenol), and acetazolamide showed K(I) values in the range of 37.5-274.5 microM for hCA I and of 0.29-113.5 microM against hCA II, respectively. All these phenols were non-competitive inhibitors with 4-nitrophenylacetate as substrate. Some antioxidant phenol derivatives investigated here showed effective hCA II inhibitory effects, in the same range as the clinically used sulfonamide acetazolamide, and might be used as leads for generating enzyme inhibitors possibly targeting other CA isoforms which have not been yet assayed for their interactions with such agents.
authors.affiliation: Ataturk University, Faculty of Sciences, Department of Chemistry, 25240-Erzurum, Turkey.
authors.forename: Murat
authors.initials: M
authors.lastname: Sentürk
authors.forename: Ilhami
authors.initials: I
authors.lastname: Gülçin
authors.forename: Arif
authors.initials: A
authors.lastname: Daştan
authors.forename: O Irfan
authors.initials: OI
authors.lastname: Küfrevioğlu
authors.forename: Claudiu T
authors.initials: CT
authors.lastname: Supuran
mesh_terms: D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology*; D024401:Carbonic Anhydrase I / Q000037:antagonists & inhibitors* / Q000097:blood / Q000737:chemistry; D024402:Carbonic Anhydrase II / Q000037:antagonists & inhibitors* / Q000097:blood / Q000737:chemistry; D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D004912:Erythrocytes / Q000201:enzymology; D006801:Humans; D010636:Phenols / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D002257:Carbonic Anhydrase Inhibitors; D010636:Phenols; D024401:Carbonic Anhydrase I; D024402:Carbonic Anhydrase II