ArticleInternational journal for parasitology. Drugs and drug resistance2015
Development and application of a sensitive, phenotypic, high-throughput image-based assay to identify compound activity against Trypanosoma cruzi amastigotes.
Article in International journal for parasitology. Drugs and drug resistance, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed.
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- Navigating drug repurposing for Chagas disease: advances, challenges, and opportunities.Frontiers in pharmacology · 2023Review
- Temporal and Wash-Out Studies Identify Medicines for Malaria Venture Pathogen Box Compounds with Fast-Acting Activity against BothMicroorganisms · 2022Article
- Paving the Way: Contributions of Big Data to Apicomplexan and Kinetoplastid Research.Frontiers in cellular and infection microbiology · 2022Review
- Past and future of trypanosomatids high-throughput phenotypic screening.Memorias do Instituto Oswaldo Cruz · 2022Article
- Antileishmanial Chemotherapy through Clemastine Fumarate Mediated Inhibition of theACS infectious diseases · 2021Article
- Antitubercular and Antiparasitic 2-Nitroimidazopyrazinones with Improved Potency and Solubility.Journal of medicinal chemistry · 2020Article
- Repurposing the open access malaria box reveals compounds with activity against Tritrichomonas foetus trophozoites.International journal for parasitology. Drugs and drug resistance · 2020Article
- Non-invasive monitoring of drug action: A new live in vitro assay design for Chagas' disease drug discovery.PLoS neglected tropical diseases · 2020Article
- The QACS infectious diseases · 2020Article
- Investigation of pyrimidine nucleoside analogues as chemical probes to assess compound effects on the proliferation of Trypanosoma cruzi intracellular parasites.PLoS neglected tropical diseases · 2020Article
- Methods for the Investigation of Trypanosoma cruzi Amastigote Proliferation in Mammalian Host Cells.Methods in molecular biology (Clifton, N.J.) · 2020Article
- ImageJ for Partially and Fully Automated Analysis of Trypanosome Micrographs.Methods in molecular biology (Clifton, N.J.) · 2020Article
- Quantitative Structure-Activity Relationships for Structurally Diverse Chemotypes Having Anti-International journal of molecular sciences · 2019Article
- Drug Discovery for Chagas Disease: Impact of Different Host Cell Lines on Assay Performance and Hit Compound Selection.Tropical medicine and infectious disease · 2019Article
- Phenothiazinium Dyes Are Active againstBioMed research international · 2019Article
- Article
Corrections and comments
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Authors and funding
2 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We have developed a high content 384-well, image-based assay to estimate the effect of compound treatment on Trypanosoma cruzi amastigotes in 3T3 fibroblasts. In the same well, the effect of compound activity on host cells can also be determined, as an initial indicator of cytotoxicity. This assay has been used to identify active compounds from an in-house library of compounds with either known biological activity or that are FDA approved, and separately, from the Medicines for Malaria Venture Malaria Box collection. Active compounds were screened against T. cruzi trypomastigotes, utilising an assay developed with the viability dye resazurin. Twelve compounds with reconfirmed solid sample activity, with IC50 values of less than 10 μM and selectivity indices to T. cruzi amastigotes over 3T3 host cells of between >22 and 319 times were identified from these libraries. As 3T3 cells are contact inhibited, with limited proliferation in the assay, selective compounds of interest were profiled in a separate assay to estimate the viability of compound treated, replicating HEK293 cells. Selective compounds that were not previously reported in the literature were further profiled by extending the incubation time against amastigote infected 3T3 cells to determine if there were residual amastigotes post-treatment, important for the consideration of the exposure time required for further biological characterisation. The assay development process and the suitability of identified compounds as hit molecules for Chagas disease research are discussed.
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