The synthesis of novel pyrazole-3,4-dicarboxamides bearing 5-amino-1,3,4-thiadiazole-2-sulfonamide moiety with effective inhibitory activity against the isoforms of human cytosolic carbonic anhydrase I and II

Mert S., Alım Z., İŞGÖR M. M., BEYDEMİR Ş., Kasımoğulları R.

Bioorganic Chemistry, vol.68, pp.64-71, 2016 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 68
  • Publication Date: 2016
  • Doi Number: 10.1016/j.bioorg.2016.07.006
  • Journal Name: Bioorganic Chemistry
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.64-71
  • Keywords: 1,3,4-Thiadiazole-2-sulfonamide, Antiglaucoma, Carbonic anhydrase, Inhibition, Pyrazole-3,4-dicarboxylic acid, Synthesis
  • Hatay Mustafa Kemal University Affiliated: Yes

Abstract

A series of 1-(3-substituted-phenyl)-5-phenyl-N3,N4-bis(5-sulfamoyl-1,3,4-thiadiazol-2-yl)-1H-pyrazole-3,4-dicarboxamides (4–15) were synthesized. The structures of these pyrazole-sulfonamides were confirmed by FT-IR, 1H NMR, 13C NMR and elemental analysis methods. Human cytosolic carbonic anhydrase (CA, EC 4.2.1.1) isozymes (hCA I and II) were purified from erythrocyte cells by affinity chromatography. The inhibitory effects of newly synthesized derivatives (4–15) were investigated in vitro on esterase activities of these isozymes. The Ki values were determined as 0.119–3.999 μM for hCA I and 0.084–0.878 μM for hCA II. The results showed that the compound 6 for hCA I and the compound 11 for hCA II had the highest inhibitory effect. Beside that, the compound 8 had the lowest inhibition effect on both isozymes.