Inhibition and binding studies of carbonic anhydrase isozymes I, II and IX with benzimidazo[1,2-c][1,2,3]thiadiazole-7-sulphonamides

Lina Baranauskiene, Mika Hilvo, Jurgita Matuliene, Dmitrij Golovenko, Elena Manakova, Virginija Dudutien, Vilma Michailovien, Jolanta Torresan, Jelena Jachno, Seppo Parkkila, Alfonso Maresca, Claudiu T. Supuran, Saulius Gražulis, Daumantas Matulis (Corresponding Author)

Research output: Contribution to journalArticleScientificpeer-review

65 Citations (Scopus)


The binding and inhibition strength of a series of benzimidazo[1,2-c][1,2, 3]thiadiazole-7-sulphonamides were determined for recombinant human carbonic anhydrase isoforms I, II, and IX. The inhibition strength was determined by a stop-flow method to measure carbon dioxide hydration. Inhibitor-enzyme binding was determined by two biophysical techniques isothermal titration calorimetry and thermal shift assay. The co-crystal structure was determined by X-ray crystallography. Comparing the results obtained using three different inhibition and binding methods increased the accuracy of compound affinity ranking and the ability to determine compound inhibitory specificity towards a particular carbonic anhydrase isoform. In most cases, all three methods yielded the same results despite using very different approaches to measure the binding and inhibition reactions. Some of the compounds studied are submicromolar inhibitors of the isoform IX, a prominent cancer target.

Original languageEnglish
Pages (from-to)863-870
Number of pages8
JournalJournal of Enzyme Inhibition and Medicinal Chemistry
Issue number6
Publication statusPublished - Dec 2010
MoE publication typeA1 Journal article-refereed


  • Carbonic anhydrase
  • Inhibition
  • Isothermal titration calorimetry
  • Sulphonamides
  • Thermal shift assay
  • X-ray crystallography


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