title: In vitro inhibition of salicylic acid derivatives on human cytosolic carbonic anhydrase isozymes I and II.
abstract: The inhibition of two human cytosolic carbonic anhydrase (hCA, EC 4.2.1.1) isozymes, hCA I and II, with a series of salicylic acid derivatives was investigated by using the esterase method with 4-nitrophenyl acetate as substrate. IC(50) values for sulfasalazine, diflunisal, 5-chlorosalicylic acid, dinitrosalicylic acid, 4-aminosalicylic acid, 4-sulfosalicylic acid, 5-sulfosalicylic acid, salicylic acid, acetylsalicylic acid (aspirin) and 3-metylsalicylic acid were of 3.04 microM, 3.38 microM, 4.07 microM, 7.64 microM, 0.13 mM, 0.29 mM, 0.42 mM, 0.56 mM, 2.71 mM and 3.07 mM for hCA I and of 4.49 microM, 2.70 microM, 0.72 microM, 2.80 microM, 0.75 mM, 0.72 mM, 0.29 mM, 0.68 mM, 1.16 mM and 4.70 mM for hCA II, respectively. Lineweaver-Burk plots were also used for the determination of the inhibition mechanism of these substituted phenols, most of which were noncompetitive inhibitors with this substrate. Some salicylic acid derivatives investigated here showed effective hCA I and II inhibitory activity, and might be used as leads for generating enzyme inhibitors eventually targeting other isoforms which have not been assayed yet for their interactions with such agents.
authors.affiliation: Ataturk University, Arts and Science Faculty, Department of Chemistry, Erzurum, Turkey.
authors.forename: Esra
authors.initials: E
authors.lastname: Bayram
authors.forename: Murat
authors.initials: M
authors.lastname: Senturk
authors.forename: O Irfan
authors.initials: OI
authors.lastname: Kufrevioglu
authors.forename: Claudiu T
authors.initials: CT
authors.lastname: Supuran
mesh_terms: D024401:Carbonic Anhydrase I / Q000037:antagonists & inhibitors* / Q000302:isolation & purification / Q000378:metabolism; D024402:Carbonic Anhydrase II / Q000037:antagonists & inhibitors* / Q000302:isolation & purification / Q000378:metabolism; D002257:Carbonic Anhydrase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D003600:Cytosol / Q000187:drug effects / Q000201:enzymology*; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D020156:Salicylic Acid / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D024401:Carbonic Anhydrase I; D024402:Carbonic Anhydrase II; D020156:Salicylic Acid