抗寄生虫苯并恶硼对体外小泰勒虫无效。

Pieter C. Steketee , Edith Paxton , Michael P. Barrett , Michael C. Pearce , Timothy K. Connelley , Liam J. Morrison
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引用次数: 0

摘要

东海岸热(ECF)是一种影响撒哈拉以南非洲牛的疾病,由蜱传Apicocomplian病原体微小泰勒氏菌引起。这种疾病是受影响地区养牛户的一个主要问题,几乎没有控制方法,包括复杂的感染和治疗疫苗、昂贵的化疗,以及通过杀螨剂更广泛地控制蜱虫。因此,迫切需要新的干预战略。苯并恶硼是一类多用途的硼杂环化合物,对多种病原体具有明显的药理活性,包括与细小T.parva有关的病原体。在本研究中,使用流式细胞术方法研究了三种苯并恶硼对细小T.parva细胞内分裂体阶段的体外疗效。在测试的苯并恶硼中,只有一种表现出任何效力,尽管只是在高浓度下,尽管与其他原生动物病原体物种相比,CPSF3蛋白靶标的蛋白质序列相似性很高。这一发现表明,目前用于治疗非洲动物锥虫病、弓形虫病、隐孢子虫病和疟疾的苯并恶硼类药物可能不适合治疗ECF。我们得出的结论是,需要对进一步的苯并恶硼化合物进行测试,以完全确定是否有任何先导化合物可以被鉴定为靶向细小T.parva。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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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, 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.

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来源期刊
CiteScore
7.90
自引率
7.50%
发文量
31
审稿时长
48 days
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.
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