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Sexual Transmission of American Trypanosomes from Males and Females to Naive Mates
Published on: January 27, 2019
Trypanosoma cruzi and Leishmania spp. CAs
Alane Beatriz Vermelho1, Felipe Raposo P Mansoldo1, Veronica Silva Cardoso1
1Bioinovar-Biotechnology Center, Institute of Microbiology Paulo de Góes, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil.
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.
Insights
Carbonic anhydrases (CAs) are promising drug targets for neglected tropical diseases like Chagas disease and leishmaniasis. Inhibitors show potent activity against parasite CAs, offering new hope for effective treatments.
Area of Science:
- Parasitology
- Drug Discovery
- Biochemistry
Background:
- Neglected tropical diseases (NTDs) like Chagas disease and leishmaniasis pose significant global health threats.
- Limited therapeutic options and increasing drug resistance in causative parasites necessitate novel treatment strategies.
Purpose of the Study:
- To investigate carbonic anhydrases (CAs) as potential drug targets against Trypanosoma cruzi and Leishmania species.
- To evaluate the efficacy and selectivity of various CA inhibitors for anti-parasitic drug development.
Main Methods:
- Functional characterization of alpha-class CA in T. cruzi (TcCA) and beta-class CA in Leishmania donovani chagasi (LdcCA).
- Screening of diverse chemical inhibitors including sulfonamides, thiols, hydroxamates, and benzoxaboroles.
- Assessment of inhibitor selectivity against human carbonic anhydrase isoforms.
- Evaluation of drug formulation strategies, such as nanoemulsions, to improve bioavailability.
Main Results:
- TcCA and LdcCA are crucial for parasite metabolism, pH regulation, and survival.
- Identified inhibitors exhibit potent enzymatic inhibition and promising selectivity for parasite CAs over human counterparts.
- Nanoemulsion formulations enhance the bioavailability and efficacy of tested compounds.
Conclusions:
- Carbonic anhydrases represent viable and selective targets for developing innovative anti-parasitic drugs.
- Targeting parasite-specific CAs, potentially in combination therapies, offers a strategic approach to combat NTDs.
- Further research into structure-activity relationships and in vivo efficacy is warranted for clinical translation.
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