Development and validation of a novel Leishmania donovani screening cascade for high-throughput screening using a novel axenic assay with high predictivity of leishmanicidal intracellular activity

by Nühs A, De Rycker M, Manthri S, Comer E, Scherer CA, Schreiber SL, Ioset JR, Gray DW, PLOS Neglected Tropical Diseases, 9(9): e0004094. doi:10.1371/journal.pntd.0004094, 2015

Summary: New drugs for visceral leishmaniasis are urgently required as existing drugs have serious shortcomings including toxicity and drug resistance. Screening large collections of chemicals (>100,000) to identify compounds that kill parasites has been used to identify new start points for drug discovery, but it is complex and expensive to look at such numbers using intracellular parasites. Parasites adapted to grow outside human cells (axenic forms) have been used in screening, but identify growth-slowing compounds as well as cidal compounds that kill parasites. A screening assay using a novel cytocidal-only axenic assay identified two new chemical series with antileishmanial activity, and activity against intracellular parasites was confirmed.

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