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

详细信息    查看全文

• 作者：Umit M. Kocyigit ; Osman Nuri Aslan ; Ilhami Gulcin ; Yusuf Temel and Mustafa Ceylan
• 刊名：Archiv der Pharmazie
• 出版年：2016
• 出版时间：December 2016
• 年：2016
• 卷：349
• 期：12
• 页码：955-963
• 全文大小：710K
• ISSN：1521-4184

文摘

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 K_i values 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 K_i values of 34.50 and 28.93 nM against the hCA I and hCA II isoenzymes, respectively.