title: Synthesis of 5-amino-1,3,4-thiadiazole-2-sulphonamide derivatives and their inhibition effects on human carbonic anhydrase isozymes.
abstract: In this study, some novel inhibitors were synthesised from the further stage reactions of 4-benzoyl-1-(4-nitrophenyl)-5-phenyl-1H-pyrazole-3-carbonyl chloride with 5-amino-1,3,4-thiadiazole-2-sulphonamide 1 (inhibitor 1). They were characterised by elemental and spectral (¹H NMR, ¹³C NMR, IR) analyses. Human carbonic anhydrase isoenzymes (hCA-I and hCA-II) were purified from erythrocyte cells by affinity chromatography. The inhibitory effects of inhibitor 1, acetazolamide (2) and the 11 newly synthesised amides (8-18) on the hydratase and esterase activities of these isoenzymes (hCA-I and hCA-II) were studied in vitro. In relation to these activities, the inhibition equilibrium constants (K(i)) were determined. The K(i) values for the new compounds (8-18) were observed to be well below that of the parent compound inhibitor 1 and were also compared to 2 under the same experimental conditions. The comparison of the newly synthesised amides to inhibitor 1 and to 2 indicated that the new derivatives preferentially inhibited hCA-II and were more potent inhibitors of hCA-II than the parent inhibitor 1 and 2.
authors.affiliation: Dumlupinar University, Faculty of Arts and Sciences, Department of Chemistry, Kutahya, Turkey. rahmikasimoglu@hotmail.com
authors.forename: Rahmi
authors.initials: R
authors.lastname: Kasımoğulları
authors.forename: Metin
authors.initials: M
authors.lastname: Bülbül
authors.forename: Samet
authors.initials: S
authors.lastname: Mert
authors.forename: Hülya
authors.initials: H
authors.lastname: Güleryüz
mesh_terms: D002256:Carbonic Anhydrases / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013830:Thiadiazoles / Q000737:chemistry
chemical_list: D004791:Enzyme Inhibitors; D013449:Sulfonamides; D013830:Thiadiazoles; C058949:1,3,4-thiadiazole; D002256:Carbonic Anhydrases