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Repurposing the open access malaria box reveals compounds with activity against Tritrichomonas foetus trophozoites.
International Journal for Parasitology: Drugs and Drug Resistance ( IF 4 ) Pub Date : 2020-06-17 , DOI: 10.1016/j.ijpddr.2020.06.003
Katy A Martin 1 , Jeba R J Jesudoss Chelladurai 1 , Christopher Bader 1 , Elizabeth Carreiro 1 , Katelyn Long 1 , Kylie Thompson 1 , Matthew T Brewer 1
Affiliation  

The protozoan parasite Tritrichomonas foetus causes early embryonic death in cattle which results in severe economic loss. In the United States, there are no drugs are approved for treatment of this pathogen. In this study, we evaluated in vitro anti-protozoal effects of compounds from an open access chemical library against T. foetus trophozoites. An initial high-throughput screen identified 16 compounds of interest. Further investigation revealed 12 compounds that inhibited parasite growth and 4 compounds with lethal effects. For lethal compounds, dose-response curves were constructed and the LD50 was calculated for laboratory and field strains of T. foetus. Our experiments revealed chemical scaffolds that were parasiticidal in the micromolar range, and these scaffolds provide a starting point for drug discovery efforts. Further investigation is still needed to investigate suitability of these scaffolds and related compounds in food animals. Importantly, open access chemical libraries can be useful for identifying compounds with activity against protozoan pathogens of veterinary importance.



中文翻译:

重新利用开放式疟疾框揭示了具有抗Trihomhomonas胎儿滋养体活性的化合物。

原生动物寄生虫Tritrichomonas胎儿引起牛的早期胚胎死亡,导致严重的经济损失。在美国,没有药物被批准用于治疗这种病原体。在这项研究中,我们评估了在体外从对开放存取的化学化合物库的抗原生动物作用T.胎儿滋养体。最初的高通量筛选确定了16种目标化合物。进一步的研究揭示了12种抑制寄生虫生长的化合物和4种具有致死作用的化合物。对于致死性化合物,绘制了剂量反应曲线,并计算了实验室和田鼠的T. fetus菌株的LD 50 。我们的实验揭示了在微摩尔范围内具有杀虫作用的化学支架,这些支架为药物发现工作提供了起点。仍需要进一步研究以研究这些支架和相关化合物在食用动物中的适用性。重要的是,开放获取化学文库可用于鉴定具有抗兽医重要原生动物病原体活性的化合物。

更新日期:2020-06-26
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