Repurposing the open access malaria box reveals compounds with activity against Tritrichomonas foetus trophozoites

Date
2020-08-01
Authors
Martin, Katy
Brewer, Matt
Jesudoss Chelladurai, Jeba
Bader, Christopher
Carreiro, Elizabeth
Long, Katelyn
Thompson, Kylie
Brewer, Matthew
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Veterinary Pathology
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Veterinary Pathology
Abstract

The protozoan parasite Tritrichomonas foetus causes early embryonic death in cattle which results in severe economic loss. In the United States, there are no drugs are approved for treatment of this pathogen. In this study, we evaluated in vitro anti-protozoal effects of compounds from an open access chemical library against T. foetus trophozoites. An initial high-throughput screen identified 16 compounds of interest. Further investigation revealed 12 compounds that inhibited parasite growth and 4 compounds with lethal effects. For lethal compounds, dose-response curves were constructed and the LD50 was calculated for laboratory and field strains of T. foetus. Our experiments revealed chemical scaffolds that were parasiticidal in the micromolar range, and these scaffolds provide a starting point for drug discovery efforts. Further investigation is still needed to investigate suitability of these scaffolds and related compounds in food animals. Importantly, open access chemical libraries can be useful for identifying compounds with activity against protozoan pathogens of veterinary importance.

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This article is published as Martin, Katy A., Jeba R.J. Jesudoss Chelladurai, Christopher Bader, Elizabeth Carreiro, Katelyn Long, Kylie Thompson, and Matthew T. Brewer. "Repurposing the open access malaria box reveals compounds with activity against Tritrichomonas foetus trophozoites." International Journal for Parasitology: Drugs and Drug Resistance 13 (2020): 89-93. DOI: 10.1016/j.ijpddr.2020.06.003. Posted with permission.

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