ArticleScientific reports2014
Nitroheterocyclic compounds are more efficacious than CYP51 inhibitors against Trypanosoma cruzi: implications for Chagas disease drug discovery and development.
Article in Scientific reports, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03587766 (Phase 2 Randomized, Multicenter, Double-blinded Safety and Efficacy Study to Evaluate Oral Fexinidazole Dosing Regimens for the Treatment of Adult Patients With Chronic Indeterminate Chagas Disease), which is not on this map. Cited by 92 papers, 3 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Phase 2 Randomized, Multicenter, Double-blinded Safety and Efficacy Study to Evaluate Oral Fexinidazole Dosing Regimens for the Treatment of Adult Patients With Chronic Indeterminate Chagas Disease
Who cites it
92 citing papers in PubMed, 3 syntheses or guidelines pooled it, 205 citations in OpenAlex.
- Listen to what the animals say: a systematic review and meta-analysis of sterol 14-demethylase inhibitor efficacy for in vivo models of Trypanosoma cruzi infection.Parasitology research · 2024Pooled it
- Monotherapy and combination chemotherapy for Chagas disease treatment: a systematic review of clinical efficacy and safety based on randomized controlled trials.Parasitology · 2022Pooled it
- Drug discovery for Chagas disease should consider Trypanosoma cruzi strain diversity.Memorias do Instituto Oswaldo Cruz · 2014Guideline
- Population pharmacokinetic-pharmacodynamic analysis of benznidazole monotherapy and combination therapy with fosravuconazole in chronic Chagas disease (BENDITA).PLoS neglected tropical diseases · 2025Trial
- Usefulness of Serial Blood Sampling and PCR Replicates for Treatment Monitoring of Patients with Chronic Chagas Disease.Antimicrobial agents and chemotherapy · 2019Trial
- Population pharmacokinetics of benznidazole in adult patients with Chagas disease.Antimicrobial agents and chemotherapy · 2015Trial
- Identification of new Trypanosoma cruzi-specific protein synthesis inhibitors by using a developed high-throughput in vitro translation assay.International journal for parasitology. Drugs and drug resistance · 2026Article
- Integrating Molecular Similarity and AlphaFold-Based Structural Alignment for Target Discovery inPharmaceuticals (Basel, Switzerland) · 2026Article
- Triazole-Functionalized Jatrophone Derivatives as Antiprotozoal Agents AgainstPharmaceuticals (Basel, Switzerland) · 2026Article
- Intermittent suppressive posaconazole therapy is ineffective at mitigating cardiac and digestive tract pathologies in an experimental model of chronic Chagas disease.Antimicrobial agents and chemotherapy · 2025Article
- Pharmacokinetic-pharmacodynamic modeling of benznidazole and its antitrypanosomal activity in a murine model of chronic Chagas disease.PLoS neglected tropical diseases · 2025Article
- Discovery and Early Optimization of 1Journal of medicinal chemistry · 2025Article
- System-based insights into parasitological and clinical treatment failure in Chagas disease.mSystems · 2025Review
- Expression Analysis of Thirteen Genes in Response to Nifurtimox and Benznidazole in Mexican Isolates of Trypanosoma cruzi by Digital PCR.Acta parasitologica · 2025Article
- New insights intoFrontiers in immunology · 2024Review
- Nanomedicines against Chagas disease: a critical review.Beilstein journal of nanotechnology · 2024Review
- Fifteen Years after the Definition ofLife (Basel, Switzerland) · 2023Review
- Short-course combination treatment for experimental chronic Chagas disease.Science translational medicine · 2023Article
- High-Throughput Phenotypic Screening and Machine Learning Methods Enabled the Selection of Broad-Spectrum Low-Toxicity Antitrypanosomatidic Agents.Journal of medicinal chemistry · 2023Article
- Further Investigations of Nitroheterocyclic Compounds as Potential Antikinetoplastid Drug Candidates.Biomolecules · 2023Review
32 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Advocacy for better drugs and access to treatment has boosted the interest in drug discovery and development for Chagas disease, a chronic infection caused by the genetically heterogeneous parasite, Trypanosoma cruzi. In this work new in vitro assays were used to gain a better understanding of the antitrypanosomal properties of the most advanced antichagasic lead and clinical compounds, the nitroheterocyclics benznidazole, nifurtimox and fexinidazole sulfone, the oxaborole AN4169, and four ergosterol biosynthesis inhibitors--posaconazole, ravuconazole, EPL-BS967 and EPL-BS1246. Two types of assays were developed: one for evaluation of potency and efficacy in dose-response against a panel of T. cruzi stocks representing all current discrete typing units (DTUs), and a time-kill assay. Although less potent, the nitroheterocyclics and the oxaborole showed broad efficacy against all T. cruzi tested and were rapidly trypanocidal, whilst ergosterol biosynthesis inhibitors showed variable activity that was both compound- and strain-specific, and were unable to eradicate intracellular infection even after 7 days of continuous compound exposure at most efficacious concentrations. These findings contest previous reports of variable responses to nitroderivatives among different T. cruzi strains and further challenge the introduction of ergosterol biosynthesis inhibitors as new single chemotherapeutic agents for the treatment of Chagas disease.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.