Pieter C. Steketee , Edith Paxton , Michael P. Barrett , Michael C. Pearce , Timothy K. Connelley , Liam J. Morrison
{"title":"抗寄生虫苯并恶硼对体外小泰勒虫无效。","authors":"Pieter C. Steketee , Edith Paxton , Michael P. Barrett , Michael C. Pearce , Timothy K. Connelley , Liam J. Morrison","doi":"10.1016/j.ijpddr.2023.10.003","DOIUrl":null,"url":null,"abstract":"<div><p>East Coast Fever (ECF) is a disease affecting cattle in sub-Saharan Africa, caused by the tick-borne Apicomplexan pathogen <em>Theileria parva</em>. 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 <em>T. parva</em>. In this study, the <em>in vitro</em> efficacy of three benzoxaboroles against the intracellular schizont stage of <em>T. parva</em> 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 <em>T. parva</em>.</p></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"23 ","pages":"Pages 71-77"},"PeriodicalIF":4.1000,"publicationDate":"2023-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Anti-parasitic benzoxaboroles are ineffective against Theileria parva in vitro\",\"authors\":\"Pieter C. Steketee , Edith Paxton , Michael P. Barrett , Michael C. Pearce , Timothy K. Connelley , Liam J. Morrison\",\"doi\":\"10.1016/j.ijpddr.2023.10.003\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>East Coast Fever (ECF) is a disease affecting cattle in sub-Saharan Africa, caused by the tick-borne Apicomplexan pathogen <em>Theileria parva</em>. 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 <em>T. parva</em>. In this study, the <em>in vitro</em> efficacy of three benzoxaboroles against the intracellular schizont stage of <em>T. parva</em> 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 <em>T. parva</em>.</p></div>\",\"PeriodicalId\":13775,\"journal\":{\"name\":\"International Journal for Parasitology: Drugs and Drug Resistance\",\"volume\":\"23 \",\"pages\":\"Pages 71-77\"},\"PeriodicalIF\":4.1000,\"publicationDate\":\"2023-10-10\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"International Journal for Parasitology: Drugs and Drug Resistance\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2211320723000337\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"PARASITOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal for Parasitology: Drugs and Drug Resistance","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2211320723000337","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PARASITOLOGY","Score":null,"Total":0}
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, 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.
期刊介绍:
The International Journal for Parasitology – Drugs and Drug Resistance is one of a series of specialist, open access journals launched by the International Journal for Parasitology. It publishes the results of original research in the area of anti-parasite drug identification, development and evaluation, and parasite drug resistance. The journal also covers research into natural products as anti-parasitic agents, and bioactive parasite products. Studies can be aimed at unicellular or multicellular parasites of human or veterinary importance.