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.

The Enzymes
|October 8, 2025
PubMed

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.

Related Concept Videos

Diversity of Protists I01:15

Diversity of Protists I

Excavata is a diverse group of protists that includes both chemoorganotrophic and phototrophic species, with some thriving in anaerobic environments. Among the key groups within Excavata are diplomonads and parabasalids, which are flagellated protists that lack mitochondria and chloroplasts. These microorganisms typically inhabit anoxic environments, such as the intestines of animals, where they exist either symbiotically or as parasites, relying on fermentation for energy production. Some...
850
Bacterial Phylum Spirochaetes01:30

Bacterial Phylum Spirochaetes

Spirochetes, unique bacteria in the phylum Spirochaetes, are gram-negative, motile, tightly coiled, slender, and flexible. They inhabit aquatic sediments and animals, with some causing diseases like syphilis. Spirochetes are classified into eight genera based on habitat, pathogenicity, phylogeny, and characteristics.Their distinctive motility arises from endoflagella, located within the cell’s periplasm. These endoflagella anchor at the cell poles and extend along the cell length, encased...
592
Diversity of Protists II01:27

Diversity of Protists II

Alveolates are a group of organisms recognized by the presence of alveoli, which are cytoplasmic sacs located beneath the cell membrane. While their function remains uncertain, alveoli may help regulate water balance by controlling how much water enters and leaves the cell. In dinoflagellates, these structures may serve as armor plates. There are three major types of alveolates: ciliates, which move using cilia; dinoflagellates, which use flagella for movement; and apicomplexans, which are...
781