ArticlePLoS neglected tropical diseases2016
Identification of Trypanocidal Activity for Known Clinical Compounds Using a New Trypanosoma cruzi Hit-Discovery Screening Cascade.
Article in PLoS neglected tropical diseases, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
What it found
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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.
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Who cites it
42 citing papers in PubMed.
- Use of P450 Enzymes for Late-Stage Functionalization in Drug Discovery.Journal of medicinal chemistry · 2025Article
- Induced pluripotent stem cell-derived human macrophages as an infection model for Trypanosoma cruzi.PLoS neglected tropical diseases · 2025Article
- Structure-activity relationships of 1,5-dihydro-2RSC medicinal chemistry · 2025Article
- Antitrypanosomal quinazolines targeting lysyl-tRNA synthetase show partial efficacy in a mouse model of acute Chagas disease.Science translational medicine · 2025Article
- System-based insights into parasitological and clinical treatment failure in Chagas disease.mSystems · 2025Review
- Identification of novel bromodomain inhibitors ofAntimicrobial agents and chemotherapy · 2024Article
- Identification of a potent and selective LAPTc inhibitor by RapidFire-Mass Spectrometry, with antichagasic activity.PLoS neglected tropical diseases · 2024Article
- Article
- Short-course combination treatment for experimental chronic Chagas disease.Science translational medicine · 2023Article
- Strasseriolides display in vitro and in vivo activity against trypanosomal parasites and cause morphological and size defects in Trypanosoma cruzi.PLoS neglected tropical diseases · 2023Article
- Frequency Variation and Dose Modification of Benznidazole Administration for the Treatment of Trypanosoma cruzi Infection in Mice, Dogs, and Nonhuman Primates.Antimicrobial agents and chemotherapy · 2023Article
- Anti-Trypanosoma cruzi activity of Coptis rhizome extract and its constituents.Tropical medicine and health · 2023Article
- Impact of Laboratory-Adapted IntracellularMicroorganisms · 2023Article
- Frequency variation and dose modification of benznidazole administration for the treatment ofbioRxiv : the preprint server for biology · 2023Article
- Navigating drug repurposing for Chagas disease: advances, challenges, and opportunities.Frontiers in pharmacology · 2023Review
- State-of-the-Art in the Drug Discovery Pathway for Chagas Disease: A Framework for Drug Development and Target Validation.Research and reports in tropical medicine · 2023Review
- Identification and development of a series of disubstituted piperazines for the treatment of Chagas disease.European journal of medicinal chemistry · 2022Article
- Synthesis and Anti-Molecules (Basel, Switzerland) · 2022Article
- Past and future of trypanosomatids high-throughput phenotypic screening.Memorias do Instituto Oswaldo Cruz · 2022Article
- The translational challenge in Chagas disease drug development.Memorias do Instituto Oswaldo Cruz · 2022Review
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
Chagas disease is a significant health problem in Latin America and the available treatments have significant issues in terms of toxicity and efficacy. There is thus an urgent need to develop new treatments either via a repurposing strategy or through the development of new chemical entities. A key first step is the identification of compounds with anti-Trypanosoma cruzi activity from compound libraries. Here we describe a hit discovery screening cascade designed to specifically identify hits that have the appropriate anti-parasitic properties to warrant further development. The cascade consists of a primary imaging-based assay followed by newly developed and appropriately scaled secondary assays to predict the cidality and rate-of-kill of the compounds. Finally, we incorporated a cytochrome P450 CYP51 biochemical assay to remove compounds that owe their phenotypic response to inhibition of this enzyme. We report the use of the cascade in profiling two small libraries containing clinically tested compounds and identify Clemastine, Azelastine, Ifenprodil, Ziprasidone and Clofibrate as molecules having appropriate profiles. Analysis of clinical derived pharmacokinetic and toxicity data indicates that none of these are appropriate for repurposing but they may represent suitable start points for further optimisation 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.