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

KOÇYİĞİT Ü. M., ASLAN O. N., GÜLÇİN İ., TEMEL Y., CEYLAN M.

ARCHIV DER PHARMAZIE, cilt.349, sa.12, ss.955-963, 2016 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 349 Sayı: 12
  • Basım Tarihi: 2016
  • Doi Numarası: 10.1002/ardp.201600092
  • Dergi Adı: ARCHIV DER PHARMAZIE
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.955-963
  • Anahtar Kelimeler: Carbonic anhydrase, Enzyme inhibition, Isoindole, Thiazole, TROUT ONCORHYNCHUS-MYKISS, ERYTHROCYTES IN-VITRO, ISOENZYMES HCA I, ACETYLCHOLINE ESTERASE, ISOZYMES I, SULFONAMIDE DERIVATIVES, ENZYME-ACTIVITY, SULFAMIDES, DISCOVERY, SERIES
  • Sivas Cumhuriyet Üniversitesi Adresli: Evet

Özet

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, H-1 NMR, C-13 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 11.80-25.81nM 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 28.93nM against the hCA I and hCA II isoenzymes, respectively.