Anti-parasitic benzoxaboroles are ineffective against Theileria parva in vitro.
Anti-parasitic benzoxaboroles are ineffective against Theileria parva in vitro.
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DOI：
10.1016/j.ijpddr.2023.10.003
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发表时间：
2023-12
影响因子：
4
通讯作者：
Morrison, Liam J.
中科院分区：
文献类型：
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作者：
Steketee, Pieter C.;Paxton, Edith;Barrett, Michael P.;Pearce, Michael C.;Connelley, Timothy K.;Morrison, Liam J.
东海岸热(ECF)是一种影响撒哈拉以南非洲牛的疾病，由壁虱传播的细小泰勒氏菌(Theileria Parva)引起。这种疾病对受影响地区的养牛户来说是一个主要问题，而且几乎没有控制方法，包括复杂的感染和治疗疫苗、昂贵的化疗，以及更广泛的通过杀螨剂控制蜱虫。因此，迫切需要新的干预策略。苯并氧硼化合物是一类用途广泛的含硼杂环化合物，对多种病原体具有明显的药理活性，包括与微小毛滴虫相关的病原体。本研究采用流式细胞术研究了三种苯并恶硼化合物对微小毛滴虫细胞内裂殖体阶段的体外抑制作用。在所测试的苯并氧硼化合物中，只有一种显示出任何效力，尽管只有在高浓度时才显示出效力，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有很高的相似性。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化合物可能不适合用于治疗ECF。我们的结论是，需要进一步测试苯并恶硼化合物，以充分确定是否有任何先导化合物可以被确定为靶向T.parva。
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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DOI：
10.1016/j.ijpddr.2019.06.004
发表时间：
2019-08-01
影响因子：
4
作者：
Nugraha, Arifin Budiman;Tuvshintulga, Bumduuren;Igarashi, Ikuo
通讯作者：
Igarashi, Ikuo
影响因子：
3.7
作者：
Hunt AG;Howe DK;Brown A;Yeargan M
通讯作者：
Yeargan M
影响因子：
6.7
作者：
Kuehl, Nikos;Lang, Johannes;Leuthold, Mila M.;Klein, Christian D.
通讯作者：
Klein, Christian D.
影响因子：
5.8
作者：
Bellini V;Swale C;Brenier-Pinchart MP;Pezier T;Georgeault S;Laurent F;Hakimi MA;Bougdour A
通讯作者：
Bougdour A
影响因子：
28.3
作者：
通讯作者：
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