title: The synthesis of novel pyrazole-3,4-dicarboxamides bearing 5-amino-1,3,4-thiadiazole-2-sulfonamide moiety with effective inhibitory activity against the isoforms of human cytosolic carbonic anhydrase I and II.
abstract: A series of 1-(3-substituted-phenyl)-5-phenyl-N(3),N(4)-bis(5-sulfamoyl-1,3,4-thiadiazol-2-yl)-1H-pyrazole-3,4-dicarboxamides (4-15) were synthesized. The structures of these pyrazole-sulfonamides were confirmed by FT-IR, (1)H NMR, (13)C NMR and elemental analysis methods. Human cytosolic carbonic anhydrase (CA, EC 4.2.1.1) isozymes (hCA I and II) were purified from erythrocyte cells by affinity chromatography. The inhibitory effects of newly synthesized derivatives (4-15) were investigated in vitro on esterase activities of these isozymes. The Ki values were determined as 0.119-3.999μM for hCA I and 0.084-0.878μM for hCA II. The results showed that the compound 6 for hCA I and the compound 11 for hCA II had the highest inhibitory effect. Beside that, the compound 8 had the lowest inhibition effect on both isozymes.
authors.affiliation: Department of Chemistry, Faculty of Arts and Sciences, Dumlupinar University, 43100 Kutahya, Turkey.
authors.forename: Samet
authors.initials: S
authors.lastname: Mert
authors.affiliation: Department of Chemistry, Faculty of Arts and Sciences, Ahi Evran University, 40000 Kırşehir, Turkey.
authors.forename: Zuhal
authors.initials: Z
authors.lastname: Alım
authors.affiliation: Department of Biochemistry, Faculty of Veterinary Sciences, Mustafa Kemal University, 31000 Hatay, Turkey.
authors.forename: Mehmet Mustafa
authors.initials: MM
authors.lastname: İşgör
authors.affiliation: Department of Chemistry, Faculty of Sciences, Atatürk University, 25240 Erzurum, Turkey; Department of Chemistry, Faculty of Natural Sciences, Architecture and Engineering, Bursa Technical University, Osmangazi, 16200 Bursa, Turkey. Electronic address: beydemir@atauni.edu.tr.
authors.forename: Şükrü
authors.initials: Ş
authors.lastname: Beydemir
authors.affiliation: Department of Chemistry, Faculty of Arts and Sciences, Dumlupinar University, 43100 Kutahya, Turkey. Electronic address: rahmi.kasimogullari@dpu.edu.tr.
authors.forename: Rahmi
authors.initials: R
authors.lastname: Kasımoğulları
mesh_terms: D024401:Carbonic Anhydrase I / Q000037:antagonists & inhibitors* / Q000378:metabolism; D024402:Carbonic Anhydrase II / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D003600:Cytosol / Q000187:drug effects* / Q000201:enzymology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D015394:Molecular Structure; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry / Q000494:pharmacology*; D013830:Thiadiazoles / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D007527:Isoenzymes; D011720:Pyrazoles; D013449:Sulfonamides; D013830:Thiadiazoles; C000620877:pyrazole-3,4-dicarboxamide; C404727:5-amino-1,3,4-thiadiazole-2-sulfonamide; D024401:Carbonic Anhydrase I; D024402:Carbonic Anhydrase II
keywords: 1,3,4-Thiadiazole-2-sulfonamide; Antiglaucoma; Carbonic anhydrase; Inhibition; Pyrazole-3,4-dicarboxylic acid; Synthesis