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, cilt.30, sa.1, ss.32-37, 2015 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 30 Sayı: 1
  • Basım Tarihi: 2015
  • Doi Numarası: 10.3109/14756366.2013.873038
  • Dergi Adı: Journal of Enzyme Inhibition and Medicinal Chemistry
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.32-37
  • Anahtar Kelimeler: Carbonic anhydrase, hydratase activity, thiadiazole, 5-AMINO-1,3,4-THIADIAZOLE-2-SULFONAMIDE DERIVATIVES, MEDICINAL CHEMISTRY, BOVINE STOMACH, PURIFICATION, ERYTHROCYTES, TARGETS, SERIES
  • Anadolu Üniversitesi Adresli: Evet

Özet

© 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.