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 (CO ) and water to bicarbonate (HCO ) 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, H NMR, C NMR, and elemental analysis. These compounds exhibited excellent inhibitory effects, in the low nanomolar range, with K 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 values of 34.50 and 28.93 nM against the hCA I and hCA II isoenzymes, respectively.

Purification of glucose-6-phosphate dehydrogenase fromrat(Rattus norvegicus)erythrocytesand inhibition effects of some metal ions on enzyme activity

“…The heavy metals transported to the waters are diluted to a high extent, partially form solid compounds such as carbonate, sulfate, and sulfur, and become highly concentrated in this region. Due to the limited adsorption capacity of the sediment layer, the heavy metal concentration in the water increases steadily –…”

Inhibitory effects of some drugs on carbonic anhydrase enzyme purified from Kangal Akkaraman sheep in Sivas, Turkey

“…CA was also purified from fish, human, and rat erythrocytes, rat saliva, cattle bones and leucocytes, and from both plants and bacteria. These purified CAs were characterized in previous studies …”

Discovery of potent carbonic anhydrase, acetylcholinesterase, and butyrylcholinesterase enzymes inhibitors: The new amides and thiazolidine-4-ones synthesized on an acetophenone base

“…The determination of activity of the CA isoforms at 348 nm was recorded by the spectrophotometric procedure of Verpoorte et al . as studied previously . According to this procedure, the absorbance changes were calculated over a period of 3 min at 25°C as p‐nitrophenylacetate was converted into 4‐nitrophenylate ions .…”