Synthesis of 5-amino-1,3,4-thiadiazole-2-sulphonamide derivatives and their inhibition effects on human carbonic anhydrase isozymes

J Enzyme Inhib Med Chem. 2011 Apr;26(2):231-7. doi: 10.3109/14756366.2010.491795. Epub 2010 Jun 16.

Abstract

In this study, some novel inhibitors were synthesised from the further stage reactions of 4-benzoyl-1-(4-nitrophenyl)-5-phenyl-1H-pyrazole-3-carbonyl chloride with 5-amino-1,3,4-thiadiazole-2-sulphonamide 1 (inhibitor 1). They were characterised by elemental and spectral (¹H NMR, ¹³C NMR, IR) analyses. Human carbonic anhydrase isoenzymes (hCA-I and hCA-II) were purified from erythrocyte cells by affinity chromatography. The inhibitory effects of inhibitor 1, acetazolamide (2) and the 11 newly synthesised amides (8-18) on the hydratase and esterase activities of these isoenzymes (hCA-I and hCA-II) were studied in vitro. In relation to these activities, the inhibition equilibrium constants (K(i)) were determined. The K(i) values for the new compounds (8-18) were observed to be well below that of the parent compound inhibitor 1 and were also compared to 2 under the same experimental conditions. The comparison of the newly synthesised amides to inhibitor 1 and to 2 indicated that the new derivatives preferentially inhibited hCA-II and were more potent inhibitors of hCA-II than the parent inhibitor 1 and 2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carbonic Anhydrases / metabolism*
  • Enzyme Activation / drug effects*
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Molecular Structure
  • Sulfonamides / chemical synthesis*
  • Sulfonamides / chemistry
  • Sulfonamides / pharmacology*
  • Thiadiazoles / chemistry

Substances

  • Enzyme Inhibitors
  • Sulfonamides
  • Thiadiazoles
  • 1,3,4-thiadiazole
  • Carbonic Anhydrases