Trypanosoma cruzi and Leishmania spp. CAs.

Abstract

Neglected tropical diseases (NTDs) such as Chagas disease and leishmaniasis represent significant public health challenges due to limited therapeutic options and the emergence of drug-resistant parasites. This chapter explores the potential of carbonic anhydrases (CAs) as novel drug targets in Trypanosoma cruzi and Leishmania spp., two etiologic agents of these diseases. The α-class CA in T. cruzi (TcCA) and the β-class CA in Leishmania donovani chagasi (LdcCA) have been functionally characterized and play essential roles in parasite metabolism, pH regulation, and survival. Several inhibitors, such as sulfonamides, thiols, hydroxamates, and benzoxaboroles, demonstrate potent enzymatic inhibition with promising selectivity over human isoforms. Advances in drug formulation, including nanoemulsions, have enhanced the bioavailability and efficacy of certain compounds. The chapter also discusses structure-activity relationships (SAR), challenges in translating in vitro potency to in vivo efficacy, and the strategic advantages of targeting parasite-specific CAs in combination therapies. These findings support CAs as viable and selective targets for innovative anti-parasitic drug development.