title: Synthesis and Carbonic Anhydrase Inhibition of Novel 2-(4-(Aryl)thiazole-2-yl)-3a,4,7,7a-tetrahydro-1H-4,7-methanoisoindole-1,3(2H)-dione Derivatives.
abstract: Carbonic anhydrase (CA, EC 4.2.1.1) is a member of the metalloenzyme family. It catalyzes the rapid conversion of carbon dioxide (CO2) and water to bicarbonate (HCO3-) and protons (H+) and also plays an important role in biochemical and physiological processes. In this study, a number of novel 2-(4-(aryl)thiazole-2-yl)-3a,4,7,7a-tetrahydro-1H-4,7-methanoisoindole-1,3(2H)-dione derivatives were synthesized and evaluated for their inhibitory characteristics against the human CA isoenzymes I and II (hCA I and hCA II). The structures of the new molecules 8a-i were confirmed by means of IR,1H NMR,13C NMR, and elemental analysis. These compounds exhibited excellent inhibitory effects, in the low nanomolar range, with Kivalues in the range of 27.07-37.80 nM against hCA I and in the range of 11.80-25.81 nM against hCA II. Our findings suggest that the new isoindolylthiazole derivatives have superior inhibitory effect over acetazolamide (AZA), which is used as clinical CA inhibitor with Kivalues of 34.50 and 28.93 nM against the hCA I and hCA II isoenzymes, respectively.
authors.affiliation: Vocational School of Health Services, Cumhuriyet University, Sivas, Turkey.
authors.forename: Umit M
authors.initials: UM
authors.lastname: Kocyigit
authors.affiliation: Department of Chemistry, Faculty of Arts and Sciences, Gaziosmanpasa University, Tokat, Turkey.
authors.forename: Osman Nuri
authors.initials: ON
authors.lastname: Aslan
authors.affiliation: Department of Chemistry, Faculty of Science, Atatürk University, Erzurum, Turkey.|Department of Zoology, College of Science, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Ilhami
authors.initials: I
authors.lastname: Gulcin
authors.affiliation: Department of Solhan School of Health Services, Bingol University, Bingol, Turkey.
authors.forename: Yusuf
authors.initials: Y
authors.lastname: Temel
authors.affiliation: Department of Chemistry, Faculty of Arts and Sciences, Gaziosmanpasa University, Tokat, Turkey.
authors.forename: Mustafa
authors.initials: M
authors.lastname: Ceylan
mesh_terms: D000086:Acetazolamide / Q000494:pharmacology; D024401:Carbonic Anhydrase I / Q000037:antagonists & inhibitors; D024402:Carbonic Anhydrase II / Q000037:antagonists & inhibitors; D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D007094:Imides / Q000494:pharmacology*; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000494:pharmacology*
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D007094:Imides; D007527:Isoenzymes; D013844:Thiazoles; D024401:Carbonic Anhydrase I; D024402:Carbonic Anhydrase II; D000086:Acetazolamide
keywords: Carbonic anhydrase; Enzyme inhibition; Isoindole; Thiazole