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Anti-parasitic benzoxaboroles are ineffective against Theileria parva in vitro
East Coast Fever (ECF) is a disease affecting cattle in sub-Saharan Africa, caused by the tick-borne Apicomplexan pathogen Theileria parva. The disease is a major problem for cattle farmers in affected regions and there are few methods of control, including a complex infection and treatment vaccine,...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10623109/ https://www.ncbi.nlm.nih.gov/pubmed/37866107 http://dx.doi.org/10.1016/j.ijpddr.2023.10.003 |
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author | Steketee, Pieter C. Paxton, Edith Barrett, Michael P. Pearce, Michael C. Connelley, Timothy K. Morrison, Liam J. |
author_facet | Steketee, Pieter C. Paxton, Edith Barrett, Michael P. Pearce, Michael C. Connelley, Timothy K. Morrison, Liam J. |
author_sort | Steketee, Pieter C. |
collection | PubMed |
description | East Coast Fever (ECF) is a disease affecting cattle in sub-Saharan Africa, caused by the tick-borne Apicomplexan pathogen Theileria parva. The disease is a major problem for cattle farmers in affected regions and there are few methods of control, including a complex infection and treatment vaccine, expensive chemotherapy, and the more widespread tick control through acaricides. New intervention strategies are, therefore, sorely needed. Benzoxaboroles are a versatile class of boron-heterocyclic compounds with demonstrable pharmacological activity against a diverse group of pathogens, including those related to T. parva. In this study, the in vitro efficacy of three benzoxaboroles against the intracellular schizont stage of T. parva was investigated using a flow cytometry approach. Of the benzoxaboroles tested, only one showed any potency, albeit only at high concentrations, even though there is high protein sequence similarity in the CPSF3 protein target compared to other protozoan pathogen species. This finding suggests that benzoxaboroles currently of interest for the treatment of African animal trypanosomiasis, toxoplasmosis, cryptosporidiosis and malaria may not be suitable for the treatment of ECF. We conclude that testing of further benzoxaborole compounds is needed to fully determine whether any lead compounds can be identified to target T. parva. |
format | Online Article Text |
id | pubmed-10623109 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-106231092023-11-04 Anti-parasitic benzoxaboroles are ineffective against Theileria parva in vitro Steketee, Pieter C. Paxton, Edith Barrett, Michael P. Pearce, Michael C. Connelley, Timothy K. Morrison, Liam J. Int J Parasitol Drugs Drug Resist Regular article East Coast Fever (ECF) is a disease affecting cattle in sub-Saharan Africa, caused by the tick-borne Apicomplexan pathogen Theileria parva. The disease is a major problem for cattle farmers in affected regions and there are few methods of control, including a complex infection and treatment vaccine, expensive chemotherapy, and the more widespread tick control through acaricides. New intervention strategies are, therefore, sorely needed. Benzoxaboroles are a versatile class of boron-heterocyclic compounds with demonstrable pharmacological activity against a diverse group of pathogens, including those related to T. parva. In this study, the in vitro efficacy of three benzoxaboroles against the intracellular schizont stage of T. parva was investigated using a flow cytometry approach. Of the benzoxaboroles tested, only one showed any potency, albeit only at high concentrations, even though there is high protein sequence similarity in the CPSF3 protein target compared to other protozoan pathogen species. This finding suggests that benzoxaboroles currently of interest for the treatment of African animal trypanosomiasis, toxoplasmosis, cryptosporidiosis and malaria may not be suitable for the treatment of ECF. We conclude that testing of further benzoxaborole compounds is needed to fully determine whether any lead compounds can be identified to target T. parva. Elsevier 2023-10-10 /pmc/articles/PMC10623109/ /pubmed/37866107 http://dx.doi.org/10.1016/j.ijpddr.2023.10.003 Text en © 2023 The Authors https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Regular article Steketee, Pieter C. Paxton, Edith Barrett, Michael P. Pearce, Michael C. Connelley, Timothy K. Morrison, Liam J. Anti-parasitic benzoxaboroles are ineffective against Theileria parva in vitro |
title | Anti-parasitic benzoxaboroles are ineffective against Theileria parva in vitro |
title_full | Anti-parasitic benzoxaboroles are ineffective against Theileria parva in vitro |
title_fullStr | Anti-parasitic benzoxaboroles are ineffective against Theileria parva in vitro |
title_full_unstemmed | Anti-parasitic benzoxaboroles are ineffective against Theileria parva in vitro |
title_short | Anti-parasitic benzoxaboroles are ineffective against Theileria parva in vitro |
title_sort | anti-parasitic benzoxaboroles are ineffective against theileria parva in vitro |
topic | Regular article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10623109/ https://www.ncbi.nlm.nih.gov/pubmed/37866107 http://dx.doi.org/10.1016/j.ijpddr.2023.10.003 |
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