Protozoans belonging to Plasmodium, Leishmania and Trypanosoma genera provoke
widespread parasitic diseases with few treatment options and many of the clinically used
drugs experiencing an extensive drug resistance phenomenon. In the last several years, the
metalloenzyme Carbonic Anhydrase (CA, EC 126.96.36.199) was cloned and characterized in the
genome of these protozoa, with the aim to search for a new drug target for fighting malaria,
leishmaniasis and Chagas disease. P. falciparum encodes for a CA (PfCA) belonging to a
novel genetic family, the η-CA class, L. donovani chagasi for a β-CA (LdcCA), whereas T.
cruzi genome contains an α-CA (TcCA). These three enzymes were characterized in detail
and a number of in vitro potent and selective inhibitors belonging to the sulfonamide, thiol,
dithiocarbamate and hydroxamate classes were discovered. Some of these inhibitors were also
effective in cell cultures and animal models of protozoan infections, making them of considerable
interest for the development of new antiprotozoan drugs with a novel mechanism of
Keywords: Carbonic anhydrases, parasitic diseases, malaria, leishmaniasis, Chagas disease, protozoa.
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