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首页> 外文期刊>Veterinary Parasitology >Repurposing of commercially available anti-coccidials identifies diclazuril and decoquinate as potential therapeutic candidates against Besnoitia besnoiti infection
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Repurposing of commercially available anti-coccidials identifies diclazuril and decoquinate as potential therapeutic candidates against Besnoitia besnoiti infection

机译：重新促使商业上可获得的抗椰子醛鉴定Diclazuril，并将其作为潜在治疗性候选人的潜在治疗候选者进行了抗癌患者

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摘要

Repurposing of currently marketed compounds with proven efficacy against apicomplexan parasites was used as an approach to define novel candidate therapeutics for bovine besnoitiosis. Besnoitia besnoiti tachyzoites grown in MARC-145 cells were exposed to different concentrations of toltrazuril, diclazuril, imidocarb, decoquinate, sulfadiazine and trimethoprim alone or in combination with sulfadiazine. Drugs were added either just prior to infection of MARC-145 cells (0 h post infection, hpi) or at 6 hpi. A primary evaluation of drug effects was done by direct immunofluorescence staining and counting. Potential effects on the host cells were assessed using a XTT kit for cell proliferation. Compounds displaying promising efficacy were selected for IC50 and IC99 determination by qPCR. In addition, the impact of drugs on the tachyzoite ultrastructure was assessed by TEM and long-term treatment assays were performed. Cytotoxicity assays confirmed that none of the compounds affected the host cells. Decoquinate and diclazuril displayed invasion inhibition rates of 90 and 83% at 0 h pi and 73 and 72% at 6 h pi, respectively. The remaining drugs showed lower efficacy and were not further studied. Decoquinate and diclazuril exhibited IC99 values of 100 nM and 29.9 mu M, respectively. TEM showed that decoquinate primarily affected the parasite mitochondrium, whilst diclazuril interfered in cytokinesis of daughter zoites. The present study demonstrates the efficacy of diclazuril and decoquinate against B. besnoid in vitro and further assessments of safety and efficacy of both drugs should be performed in the target species.
机译：将目前销售的化合物的重新促销与ApiCoMplexan寄生虫的经过验证的疗效被用作定义新颖的BENOitiens的新候选治疗方法的方法。 Besnoitia Besnoiti Tachyzoites在Marc-145细胞中生长，暴露于不同浓度的托拉唑尔，Diclazuril，Imidocarb，脱核，磺胺腈和三甲硅皮，或与磺胺扎嗪组合。在感染MARC-145细胞（0 H后感染，HPI）或6 HPI之前，添加药物。通过直接免疫荧光染色和计数进行药物效应的初步评估。使用XTT试剂盒进行细胞增殖评估对宿主细胞的潜在影响。选择显示有希望功效的化合物用于IC50和IC99通过QPCR测定。此外，通过TEM和长期治疗测定评估药物对Tachyzoite超微结构的影响。细胞毒性测定证实，这些化合物没有影响宿主细胞。将侵蚀性和Diclazuril在0h Pi和73％的侵袭抑制率为90％和83％，分别为6小时，73％和72％。其余药物表现出较低的功效，并且没有进一步研究。 Deocoinate和Diclazuril分别显示IC99值100nm和29.9 mu m。 TEM表明，腐殖质主要影响寄生虫线粒体，虽然Diclazuril干扰了女儿Zoites的细胞因子。本研究证明了Diclazuril和Decoinate对B. BERNOID体外的疗效以及两种药物的安全性和疗效的进一步评估应在目标物种中进行。

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