Targeting Carbonic Anhydrases from Trypanosoma cruzi and Leishmania spp. as a Therapeutic Strategy to Obtain New Antiprotozoal Drugs

Abstract

Chagas disease and leishmaniasis are potentially life-threatening disorders, included in the list of neglected tropical diseases (NTD) by the World Health Organization. Trypanosoma cruzi and Leishmania spp. are protozoa of the Trypanosomatidae family, that are the etiological agents of the two parasitosis. The latter are also spreading significantly to Europe and North America, making urgent a concrete intervention from the healthcare systems of the developed countries. Carbonic anhydrases (CAs, EC 4.2.1.1) belonging to the α- and β-class were recently identified in these protozoans and shown to be essential in the pathogen physiology and pathogenicity with roles in growth, acclimatization, and virulence development. The α-CA from T. cruzi (TcCA) and the β-CA from L. donovani chagasi (LdccCA) have been recognized as new enzymatic targets for an antiinfective intervention overcoming the cross-resistance to existing drugs. This chapter gathered the state of the art on biochemistry and pharmacology of both protozoan CAs. All known inhibitors of TcCA and LdcCA are here illustrated and discussed in detail as for in vitro enzyme inhibition and in cell antiprotozoal action against multiple strains and developmental forms of T. cruzi and Leishmania.