ArticlePLoS neglected tropical diseases2014
Benznidazole biotransformation and multiple targets in Trypanosoma cruzi revealed by metabolomics.
Article in PLoS neglected tropical diseases, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 115 citations in OpenAlex.
- The fecal, oral, and skin microbiota of children with Chagas disease treated with benznidazole.PloS one · 2019Trial
- Overcoming Trypanosoma cruzi persistence with a mechanistically distinct drug combination.npj antimicrobials and resistance · 2026Article
- Adverse reactions to etiological treatment in patients with Chagas disease in the Western Potiguar mesoregion of Brazil: a cross-sectional study.Sao Paulo medical journal = Revista paulista de medicina · 2026Observational
- Transcriptomic Analysis of Trypanosomatids.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Advances and challenges in the search for new treatments for Chagas disease.Memorias do Instituto Oswaldo Cruz · 2026Review
- Glycosomal ABC transporter 3 (GAT3) deletion enhances the oxidative stress responses and reduces the infectivity of Trypanosoma cruzi.PLoS neglected tropical diseases · 2025Article
- Untargeted Metabolomics of Epimastigote Forms ofBio-protocol · 2025Article
- TrypPROTACs Unlocking New Therapeutic Strategies for Chagas Disease.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Exploring the mechanisms of action of the antimicrobial peptide CZS-5 against Trypanosoma cruzi epimastigotes: insights from metabolomics and molecular dynamics.Parasites & vectors · 2025Article
- Pharmacokinetic-pharmacodynamic modeling of benznidazole and its antitrypanosomal activity in a murine model of chronic Chagas disease.PLoS neglected tropical diseases · 2025Article
- System-based insights into parasitological and clinical treatment failure in Chagas disease.mSystems · 2025Review
- Nanomedicines against Chagas disease: a critical review.Beilstein journal of nanotechnology · 2024Review
- Transcriptomic analysis of benznidazole-resistant and susceptible Trypanosoma cruzi populations.Parasites & vectors · 2023Article
- The critical role of mode of action studies in kinetoplastid drug discovery.Frontiers in drug discovery · 2023Article
- Population pharmacokinetics of benznidazole in neonates, infants and children using a new pediatric formulation.PLoS neglected tropical diseases · 2023Article
- Impact of Laboratory-Adapted IntracellularMicroorganisms · 2023Article
- New Insights into the Role of thePathogens (Basel, Switzerland) · 2023Article
- Disruption of multiple copies of the Prostaglandin F2alpha synthase gene affects oxidative stress response and infectivity in Trypanosoma cruzi.PLoS neglected tropical diseases · 2022Article
- Article
- Genetic and pharmacological evidence for kinetic competition between alternative poly(A) sites in yeast.eLife · 2021Article
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Authors and funding
5 authors at 3 institutions in 3 countries.
Funding
Abstract
backgroundThe first line treatment for Chagas disease, a neglected tropical disease caused by the protozoan parasite Trypanosoma cruzi, involves administration of benznidazole (Bzn). Bzn is a 2-nitroimidazole pro-drug which requires nitroreduction to become active, although its mode of action is not fully understood. In the present work we used a non-targeted MS-based metabolomics approach to study the metabolic response of T. cruzi to Bzn. METHODOLOGY/PRINCIPAL
findingsParasites treated with Bzn were minimally altered compared to untreated trypanosomes, although the redox active thiols trypanothione, homotrypanothione and cysteine were significantly diminished in abundance post-treatment. In addition, multiple Bzn-derived metabolites were detected after treatment. These metabolites included reduction products, fragments and covalent adducts of reduced Bzn linked to each of the major low molecular weight thiols: trypanothione, glutathione, γ-glutamylcysteine, glutathionylspermidine, cysteine and ovothiol A. Bzn products known to be generated in vitro by the unusual trypanosomal nitroreductase, TcNTRI, were found within the parasites, but low molecular weight adducts of glyoxal, a proposed toxic end-product of NTRI Bzn metabolism, were not detected. CONCLUSIONS/SIGNIFICANCE: Our data is indicative of a major role of the thiol binding capacity of Bzn reduction products in the mechanism of Bzn toxicity against T. cruzi.
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