1 research outputs found
Cloning, Characterization, and Sulfonamide and Thiol Inhibition Studies of an α‑Carbonic Anhydrase from <i>Trypanosoma cruzi</i>, 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 <i>Trypanosoma
cruzi</i>, the causative agent of Chagas disease. The enzyme
(TcCA) has a very high catalytic activity for the CO<sub>2</sub> 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 (<i>K</i><sub>I</sub> values of 192 nM to
84 μM), whereas some heterocyclic compounds inhibited the enzyme
with <i>K</i><sub>I</sub> values in the range 61.6–93.6
nM. The thiols were the most potent in vitro inhibitors (<i>K</i><sub>I</sub> values of 21.1–79.0 nM), and some of them also
inhibited the epimastigotes growth of two <i>T. cruzi</i> strains in vivo