Evaluation of the growth-inhibitory effect of trifluralin analogues on in vitro cultured Babesia bovis parasites
Evaluation of the growth-inhibitory effect of trifluralin analogues on in vitro cultured Babesia bovis parasites
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DOI：
10.1016/j.ijpddr.2013.01.003
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发表时间：
2013-12-01
影响因子：
4
通讯作者：
Suarez, Carlos E.
中科院分区：
文献类型：
--
作者：
Silva, Marta G.;Domingos, Ana;Suarez, Carlos E.
牛巴贝斯虫病是由牛巴贝斯虫引起的一种全球性蜱传血原虫寄生虫病，其特征为发热、贫血、体重减轻并最终死亡。已经在牛中使用多年的几种杀巴贝斯药物已被证明仅部分有效，并且需要开发针对巴贝斯虫病的高度特异性和低毒性的替代化疗药物。氟乐灵衍生物特异性结合植物和原生动物寄生虫中的α-微管蛋白，导致生长抑制。一组12氟乐灵类似物（TFLA）先前已被证明是抑制利什曼原虫种的生长。利什曼原虫和B. bovis提供了测试这些化合物也作为巴贝杀螨剂的基本原理。除了三种新的TFLA（称为TFLA 13-15）之外，还针对体外培养的B测试了先前测试的利什曼原虫抑制剂TFLA 1-12减去TFLA 5。牛寄生虫而在研究中测试的所有TFLA均显示出对B的抑制。牛体外生长TFLA 7、TFLA 10和TFLA 13是最有效的抑制剂，对于生物减毒的克隆B，72小时时的估计IC 50（μ M）分别为8.5 +/-0.3; 9.2 +/-0.2; 8.9 +/-0.7。牛Mo 7株和强毒B分别为13.6 ± 1.5、18.7 ± 1.6和10.6 ± 1.9。牛T（3）Bo株。两种菌株之间的差异无统计学显著性。重要的是，这些药物在测试剂量下对宿主红细胞和牛肾动脉内皮细胞显示出低水平的毒性。氟乐灵类似物抑制B体外生长的能力已得到证实。牛寄生虫以及它们对宿主细胞的低毒性表明这些化合物可以进一步开发作为治疗牛巴贝西虫病的新的替代物。(C)2013年澳大利亚寄生虫学会。由爱思唯尔有限公司出版。保留所有权利。
Bovine babesiosis, caused by Babesia bovis, is a global tick borne hemoprotozoan parasite disease characterized by fever, anemia, weight losses and ultimately death. Several babesicidal drugs that have been in use in cattle for years have proven to be only partially effective and the development of alternative chemotherapeutics that are highly specific and have low toxicity against babesiosis is needed. Trifluralin derivatives specifically bind alpha-tubulin in plants and protozoa parasites causing growth inhibition. A set of 12 trifluralin analogues (TFLA) has previously been shown to be inhibitory for the growth of Leishmania species. The conservation of several key amino acids involved in the trifluralin binding site of alpha-tubulin among Leishmania sp. and B. bovis provides rationale for testing these compounds also as babesiacides. The previously tested Leishmania inhibitory, TFLA 1-12 minus TFLA 5, in addition to three novel TFLA (termed TFLA 13-15), were tested against in vitro cultured B. bovis parasites. While all of the TFLA tested in the study showed inhibition of B. bovis growth in vitro TFLA 7, TFLA 10 and TFLA 13, were the most effective inhibitors with estimated IC50 (mu M) at 72 h of 8.5 +/- 0.3; 9.2 +/- 0.2; 8.9 +/- 0.7, respectively for the biologically attenuated cloned B. bovis Mo7 strain, and 13.6 +/- 1.5; 18.7 +/- 1.6; 10.6 +/- 1.9, respectively for the virulent B. bovis T(3)Bo strain. The differences found between the two strains were not statistically significant. Importantly, these drugs displayed low levels of toxicity for the host erythrocytes and bovine renal arterial endothelial cells at the doses tested. The demonstrated ability of trifluralin analogues to inhibit in vitro growth of B. bovis parasites combined with their low toxicity for host cells suggests that these compounds may be further developed as novel alternatives for the treatment of bovine babesiosis. (C) 2013 Australian Society for Parasitology. Published by Elsevier Ltd. All rights reserved.