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

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 acces...

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Autores principales: Martin, Katy A., Jesudoss Chelladurai, Jeba R.J., Bader, Christopher, Carreiro, Elizabeth, Long, Katelyn, Thompson, Kylie, Brewer, Matthew T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7326994/
https://www.ncbi.nlm.nih.gov/pubmed/32734889
http://dx.doi.org/10.1016/j.ijpddr.2020.06.003
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author Martin, Katy A.
Jesudoss Chelladurai, Jeba R.J.
Bader, Christopher
Carreiro, Elizabeth
Long, Katelyn
Thompson, Kylie
Brewer, Matthew T.
author_facet Martin, Katy A.
Jesudoss Chelladurai, Jeba R.J.
Bader, Christopher
Carreiro, Elizabeth
Long, Katelyn
Thompson, Kylie
Brewer, Matthew T.
author_sort Martin, Katy A.
collection PubMed
description 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 LD(50) 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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spelling pubmed-73269942020-07-06 Repurposing the open access malaria box reveals compounds with activity against Tritrichomonas foetus trophozoites Martin, Katy A. Jesudoss Chelladurai, Jeba R.J. Bader, Christopher Carreiro, Elizabeth Long, Katelyn Thompson, Kylie Brewer, Matthew T. Int J Parasitol Drugs Drug Resist Article 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 LD(50) 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. Elsevier 2020-06-17 /pmc/articles/PMC7326994/ /pubmed/32734889 http://dx.doi.org/10.1016/j.ijpddr.2020.06.003 Text en © 2020 Published by Elsevier Ltd on behalf of Australian Society for Parasitology. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Martin, Katy A.
Jesudoss Chelladurai, Jeba R.J.
Bader, Christopher
Carreiro, Elizabeth
Long, Katelyn
Thompson, Kylie
Brewer, Matthew T.
Repurposing the open access malaria box reveals compounds with activity against Tritrichomonas foetus trophozoites
title Repurposing the open access malaria box reveals compounds with activity against Tritrichomonas foetus trophozoites
title_full Repurposing the open access malaria box reveals compounds with activity against Tritrichomonas foetus trophozoites
title_fullStr Repurposing the open access malaria box reveals compounds with activity against Tritrichomonas foetus trophozoites
title_full_unstemmed Repurposing the open access malaria box reveals compounds with activity against Tritrichomonas foetus trophozoites
title_short Repurposing the open access malaria box reveals compounds with activity against Tritrichomonas foetus trophozoites
title_sort repurposing the open access malaria box reveals compounds with activity against tritrichomonas foetus trophozoites
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7326994/
https://www.ncbi.nlm.nih.gov/pubmed/32734889
http://dx.doi.org/10.1016/j.ijpddr.2020.06.003
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