A novel in vitro image-based assay identifies new drug leads for giardiasis
- PMID: 28171818
- PMCID: PMC5295624
- DOI: 10.1016/j.ijpddr.2017.01.005
A novel in vitro image-based assay identifies new drug leads for giardiasis
Abstract
Giardia duodenalis is an intestinal parasite that causes giardiasis, a widespread human gastrointestinal disease. Treatment of giardiasis relies on a small arsenal of compounds that can suffer from limitations including side-effects, variable treatment efficacy and parasite drug resistance. Thus new anti-Giardia drug leads are required. The search for new compounds with anti-Giardia activity currently depends on assays that can be labour-intensive, expensive and restricted to measuring activity at a single time-point. Here we describe a new in vitro assay to assess anti-Giardia activity. This image-based assay utilizes the Perkin-Elmer Operetta® and permits automated assessment of parasite growth at multiple time points without cell-staining. Using this new approach, we assessed the "Malaria Box" compound set for anti-Giardia activity. Three compounds with sub-μM activity (IC50 0.6-0.9 μM) were identified as potential starting points for giardiasis drug discovery.
Keywords: Drug discovery; Giardia; Image-based assay; Malaria Box.
Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.
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References
-
- Al-Mekhlafi M.S., Azlin M., Nor Aini U., Shaik A., Sa'iah A., Fatmah M.S., Ismail M.G., Ahmad Firdaus M.S., Aisah M.Y., Rozlida A.R., Norhayati M. Giardiasis as a predictor of childhood malnutrition in Orang Asli children in Malaysia. Trans. R. Soc. Trop. Med. Hyg. 2005;99:686–691. - PubMed
-
- Ansell B.R., McConville M.J., Ma'ayeh S.Y., Dagley M.J., Gasser R.B., Svard S.G., Jex A.R. Drug resistance in Giardia duodenalis. Biotechnol. Adv. 2015;33:888–901. - PubMed
-
- Arguello-Garcia R., Cruz-Soto M., Romero-Montoya L., Ortega-Pierres G. Variability and variation in drug susceptibility among Giardia duodenalis isolates and clones exposed to 5-nitroimidazoles and benzimidazoles in vitro. J. Antimicrob. Chemother. 2004;54:711–721. - PubMed
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