Carbonic anhydrases from Trypanosoma and Leishmania as anti-protozoan drug targets.
Trypanosoma cruzi and Leishmania spp. are protozoa of the Trypanosomatidae family, being the etiological agents of two widespread parasitic diseases, Chagas disease and leishmaniasis, respectively. Both parasites are the focus of worldwide research with the aim to find effective and less toxic drugs than the few ones available so far, and for controlling the spread of the diseases. Carbonic anhydrases (CAs, EC 4.2.1.1) belonging to the α- and β-class were recently identified in these protozoans and several studies suggested that they could be new targets for drug development. Sulfonamide, thiol and hydroxamate inhibitors effectively inhibited the α-CA from T. cruzi (TcCA) and the β-CA from L. donovani chagasi (LdccCA) in vitro, and some of them also showed in vivo efficacy in inhibiting the growth of the parasites in animal models of Chagas disease and leishmaniasis. As few therapeutic options are presently available for these orphan diseases, protozoan CA inhibition may represent a novel strategy to address this stringent health problem.
BIOINOVAR - Biotechnology Laboratories: Biocatalysis, Bioproducts and Bioenergy, Institute of Microbiology Paulo de Goes, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. Electronic address: abvermelho@micro.ufrj.br.
Alane B
AB
Vermelho
School of Science and Technology and Graduate Studies in Science Education Program, University of Rio Grande, Duque de Caxias, RJ, Brazil.
Giseli R
GR
Capaci
Department of Natural Products and Food, School of Pharmacy, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
Igor A
IA
Rodrigues
BIOINOVAR - Biotechnology Laboratories: Biocatalysis, Bioproducts and Bioenergy, Institute of Microbiology Paulo de Goes, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Verônica S
VS
Cardoso
BIOINOVAR - Biotechnology Laboratories: Biocatalysis, Bioproducts and Bioenergy, Institute of Microbiology Paulo de Goes, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Ana Maria
AM
Mazotto
Neurofarba Department and Laboratorio di Chimica Bioinorganica, Università degli Studi di Firenze, Via U. Schiff 6, 50019 Sesto Fiorentino, Florence, Italy. Electronic address: claudiu.supuran@unifi.it.
Claudiu T
CT
Supuran
D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D002256:Carbonic Anhydrases / Q000187:drug effects* / Q000378:metabolism; D007891:Leishmania / Q000187:drug effects* / Q000201:enzymology / Q000254:growth & development; D014349:Trypanosoma cruzi / Q000187:drug effects* / Q000201:enzymology / Q000254:growth & development
D000981:Antiprotozoal Agents; D002256:Carbonic Anhydrases
Anti-infectives; Carbonic anhydrase; Hydroxamate; Inhibitor; Leishmania spp.; Sulfonamide; Trypanosoma cruzi