title: Evaluating the developmental toxicity of trypanocidal nitroaromatic compounds on zebrafish.
abstract: Current therapies against African and American trypanosomiasis are problematic and with no immediate prospect of a vaccine there is an urgent need for cheap, more effective treatments. To aid the drug discovery pipeline, we report a novel in vivo screening approach using zebrafish (Danio rerio) embryos as a means of rapidly assessing a compounds developmental toxicity. This technique, amenable to high-throughput screening, was validated using several trypanocidal nitroaromatic prodrugs including nifurtimox and benznidazole.
authors.affiliation: School of Biological and Chemical Sciences, Queen Mary University of London, Mile End Road, London E1 4NS, UK.
authors.forename: Grace
authors.initials: G
authors.lastname: Buchanan-Kilbey
authors.forename: Joshua
authors.initials: J
authors.lastname: Djumpah
authors.forename: Maria V
authors.initials: MV
authors.lastname: Papadopoulou
authors.forename: William
authors.initials: W
authors.lastname: Bloomer
authors.forename: Lonqin
authors.initials: L
authors.lastname: Hu
authors.forename: Shane R
authors.initials: SR
authors.lastname: Wilkinson
authors.forename: Rachel
authors.initials: R
authors.lastname: Ashworth
mesh_terms: D000818:Animals; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D004625:Embryo, Nonmammalian / Q000187:drug effects*; D057166:High-Throughput Screening Assays / Q000379:methods; D009547:Nifurtimox / Q000009:adverse effects; D009593:Nitroimidazoles / Q000009:adverse effects; D014344:Trypanocidal Agents / Q000009:adverse effects*; D015027:Zebrafish / Q000196:embryology*
chemical_list: D009593:Nitroimidazoles; D014344:Trypanocidal Agents; D009547:Nifurtimox; C009999:benzonidazole
keywords: Development; Protozoa; Toxicity; Trypanosome; Zebrafish