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Synthesis and Carbonic Anhydrase Inhibition of Novel 2‐(4‐(Aryl)thiazole‐2‐yl)‐3a,4,7,7a‐tetrahydro‐1 H ‐4,7‐methanoisoindole‐1,3(2 H )‐dione Derivatives
Author(s) -
Kocyigit Umit M.,
Aslan Osman Nuri,
Gulcin Ilhami,
Temel Yusuf,
Ceylan Mustafa
Publication year - 2016
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.201600092
Subject(s) - carbonic anhydrase , chemistry , thiazole , acetazolamide , carbonic anhydrase i , aryl , bicarbonate , stereochemistry , proton nmr , carbonic anhydrase ii , isozyme , carbon 13 nmr , enzyme , medicinal chemistry , biochemistry , organic chemistry , medicine , alkyl , anesthesia
Carbonic anhydrase (CA, EC 4.2.1.1) is a member of the metalloenzyme family. It catalyzes the rapid conversion of carbon dioxide (CO 2 ) and water to bicarbonate (HCO 3 − ) 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‐1 H ‐4,7‐methanoisoindole‐1,3(2 H )‐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, 1 H NMR, 13 C 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.