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重新利用开放获取的疟疾药物库发现了具有抗滴虫滋养体活性的化合物。

Repurposing the open access malaria box reveals compounds with activity against Tritrichomonas foetus trophozoites.

机构信息

Department of Veterinary Pathology, College of Veterinary Medicine, Iowa State University, Ames, IA, USA.

Department of Veterinary Pathology, College of Veterinary Medicine, Iowa State University, Ames, IA, USA.

出版信息

Int J Parasitol Drugs Drug Resist. 2020 Aug;13:89-93. doi: 10.1016/j.ijpddr.2020.06.003. Epub 2020 Jun 17.

Abstract

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 LD 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.

摘要

纤毛原虫寄生虫胎儿三毛滴虫导致牛的早期胚胎死亡,造成严重的经济损失。在美国,没有批准用于治疗这种病原体的药物。在这项研究中,我们评估了从开放获取化学文库中化合物对胎儿三毛滴虫滋养体的体外抗原生动物作用。初步的高通量筛选确定了 16 种有意义的化合物。进一步的研究表明,有 12 种化合物能抑制寄生虫的生长,有 4 种化合物有致死作用。对于致死化合物,构建了剂量-反应曲线,并计算了实验室和田间菌株胎儿三毛滴虫的 LD。我们的实验揭示了在微摩尔范围内具有杀寄生虫作用的化学支架,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,开放获取的化学文库可用于鉴定对兽医重要的原生动物病原体具有活性的化合物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e4cd/7326994/0547a24cd881/fx1.jpg

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