A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Cloning, Characterization, and Sulfonamide and Thiol Inhibition Studies of an α-Carbonic Anhydrase from Trypanosoma cruzi, the Causative Agent of Chagas Disease
Tekijät: Pan Peiwen; Vermelho Alane Beatriz; Capaci Rodrigues Giseli; Scozzafava Andrea; Tolvanen Martti E. E.; Parkkila Seppo; Capasso Clemente; Supuran Claudiu T.
Kustantaja: American Chemical Society (ACS)
Julkaisuvuosi: 2013
Lehti:Journal of Medicinal Chemistry
Tietokannassa oleva lehden nimiJournal of Medicinal Chemistry
Lehden akronyymi: J Med Chem
Vuosikerta: 56
Numero: 4
Aloitussivu: 1761
Lopetussivu: 1771
ISSN: 0022-2623
eISSN: 1520-4804
DOI: https://doi.org/10.1021/jm4000616
Verkko-osoite: https://doi.org/10.1021/jm4000616
Tiivistelmä
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 CO2 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.
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 CO2 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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