Untargeted metabolomics for triaging of cytochrome b inhibitors during Chagas’ disease drug discovery
PLOS Neglected Tropical Diseases·
- DOI
- 10.1371/journal.pntd.0013917
- PMID
- 41557738
- PMCID
- PMC12844530
- OpenAlex
- W7125168055
- Study type
- Journal article
- Publisher
- Public Library of Science (PLoS)
- Article type
- journal-article
- Integrity
- current
Why this research matters now
The proposed metabolomics-based counter-screening approach could be implemented early in Chagas' disease drug discovery workflows to prioritize compounds with novel mechanisms of action, addressing the urgent need for new treatments.
Structured evidence summary
Research question
Whether untargeted metabolomics can identify and triage cytochrome b inhibitors among phenotypic screening hits during Chagas' disease drug discovery.
Study design
Laboratory-based metabolomics study using liquid chromatography mass spectrometry (LC-MS) to profile metabolite changes in cultured epimastigote-form Trypanosoma cruzi following treatment with cytochrome b inhibitors and comparator compounds.
Population and setting
In vitro culture of epimastigote-form Trypanosoma cruzi, the causative agent of Chagas' disease.
Main findings
Cytochrome b inhibitors produced rapid and pronounced metabolomic perturbation in cultured T. cruzi. A signature of 79 differentially expressed metabolites (≥2-fold change, p < 0.05) distinguished cytochrome b inhibitors from compounds acting through other modes of action, including other mechanisms disrupting oxidative phosphorylation. The signature showed flexibility across experiments and compound sets.
Public-health relevance
The proposed metabolomics-based counter-screening approach could be implemented early in Chagas' disease drug discovery workflows to prioritize compounds with novel mechanisms of action, addressing the urgent need for new treatments.
Important limitations
The summary is limited to the supplied single-article abstract and bibliographic metadata; the original paper is required for decision-grade interpretation of the methodology, validation, and generalizability of the proposed metabolomics signature.
GIDS interpretation
This article is discoverable through its focus on Chagas' disease treatment and drug discovery methodology. No connection to a live surveillance signal is made based on the supplied evidence.
Related GIDS surveillance
Literature context does not validate, explain, or change a surveillance signal. Exact and contextual relationships are shown separately.
Evidence relationships
This article has 5 auditable classifier relationships to diseases, places, topics, and study design.