Synthesis and evaluation of new thiadiazole derivatives as potential inhibitors of human carbonic anhydrase isozymes (hCA-I and hCA-II)

ALTINTOP M. D., ÖZDEMİR A., Kucukoglu K., Turan-Zitouni G., NADAROĞLU H., KAPLANCIKLI Z. A.

Journal of Enzyme Inhibition and Medicinal Chemistry, vol.30, no.1, pp.32-37, 2015 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 30 Issue: 1
  • Publication Date: 2015
  • Doi Number: 10.3109/14756366.2013.873038
  • Journal Name: Journal of Enzyme Inhibition and Medicinal Chemistry
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.32-37
  • Keywords: Carbonic anhydrase, hydratase activity, thiadiazole, 5-AMINO-1,3,4-THIADIAZOLE-2-SULFONAMIDE DERIVATIVES, MEDICINAL CHEMISTRY, BOVINE STOMACH, PURIFICATION, ERYTHROCYTES, TARGETS, SERIES
  • Bilecik Şeyh Edebali University Affiliated: No

Abstract

© 2014 Informa UK Ltd.2-[[5-(2,4-Difluoro/dichlorophenylamino)-1,3,4-thiadiazol-2-yl]thio] acetophenone derivatives (3a-s) were designed as human carbonic anhydrase isozymes (hCA-I and hCA-II) inhibitors and synthesized. hCA-I and hCA-II were purified from erythrocyte cells by the affinity chromatography. The inhibitory effects of 18 newly synthesized acetophenones on hydratase activity of these isoenzymes were studied in vitro. The average IC50 values of the new compounds for hydratase activity ranged from 0.033 to 0.14 μM for hCA-I and from 0.030 to 0.11 μM for hCA-II. Among the newly synthesized compounds, 2-[[5-(2,4-dichlorophenylamino)-1,3,4-thiadiazol-2-yl]thio]-4′-bromoacetophenone (3n) can be considered as a promising hCA-II inhibitor owing to its selective and potent inhibitory effect on hCA-II.