A novel in vitro image-based assay identifies new drug leads for giardiasis

摘要

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^(R) 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-@mM activity (IC"5"0 0.6-0.9 @mM) were identified as potential starting points for giardiasis drug discovery.