A novel in vitro image-based assay identifies new drug leads for giardiasis. Issue 1 (April 2017)

• Record Type: Journal Article
• Authors: Hart, Christopher J.S.; Munro, Taylah; Andrews, Katherine T.; Ryan, John H.; Riches, Andrew G.; Skinner-Adams, Tina S.
• Is Part Of: International journal for parasitology. Volume 7:Issue 1(2017)
• Page Start: 83
• Page End: 89
• Publication Date: 2017-04
• Subjects: Giardia -- Drug discovery -- Malaria Box -- Image-based assay; Parasitic diseases -- Chemotherapy -- Periodicals; Drug resistance -- Periodicals; 616.96061
• DOI: 10.1016/j.ijpddr.2017.01.005
• Languages: English
• ISSNs: 2211-3207

Abstract

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. Graphical abstract: Highlights: We describe a new automated image-based method to enumerate Giardia trophozoites. This method permits the assessment of parasite growth at multiple time points without staining. The "Malaria Box" compound set was assessed for anti- Giardia activity using this approach. Three compounds with sub-μM activity were identified.