Cloning, Characterization, and Sulfonamide and Thiol Inhibition Studies of an α-Carbonic Anhydrase from Trypanosoma cruzi, the Causative Agent of Chagas Disease.
An α-carbonic anhydrase (CA, EC 4.2.1.1) has been identified, cloned, and characterized from the unicellular protozoan Trypanosoma cruzi, the causative agent of Chagas disease. The enzyme (TcCA) has a very high catalytic activity for the CO(2) hydration reaction, being similar kinetically to the human (h) isoform hCA II, although it is devoid of the His64 proton shuttle. A large number of aromatic/heterocyclic sulfonamides and some 5-mercapto-1,3,4-thiadiazoles were investigated as TcCA inhibitors. The aromatic sulfonamides were weak inhibitors (K(I) values of 192 nM to 84 μM), whereas some heterocyclic compounds inhibited the enzyme with K(I) values in the range 61.6-93.6 nM. The thiols were the most potent in vitro inhibitors (K(I) values of 21.1-79.0 nM), and some of them also inhibited the epimastigotes growth of two T. cruzi strains in vivo.
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GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL GENE-Y
CA EC 4.2.1.1 hCA II α-carbonic anhydrase TcCA α-Carbonic Anhydrase CO(2) His aromatic/heterocyclic sulfonamides 5-mercapto-1,3,4-thiadiazoles aromatic sulfonamides thiols Sulfonamide Thiol TcCA