内啡肽样喹诺酮-300 和 ELQ-316 抑制牛巴贝斯虫、双芽巴贝斯虫、马巴贝斯虫和马媾疫锥虫。
Endochin-like quinolone-300 and ELQ-316 inhibit Babesia bovis, B. bigemina, B. caballi and Theileria equi.
机构信息
Department of Veterinary Microbiology and Pathology, College of Veterinary Medicine, Washington State University, Pullman, WA, USA.
Oregon Health and Science University, 3181 SW Sam Jackson Blvd., Portland, Oregon, 97239, USA.
出版信息
Parasit Vectors. 2020 Dec 3;13(1):606. doi: 10.1186/s13071-020-04487-3.
BACKGROUND
The most common apicomplexan parasites causing bovine babesiosis are Babesia bovis and B. bigemina, while B. caballi and Theileria equi are responsible for equine piroplasmosis. Treatment and control of these diseases are usually achieved using potentially toxic chemotherapeutics, such as imidocarb diproprionate, but drug-resistant parasites are emerging, and alternative effective and safer drugs are needed. The endochin-like quinolones (ELQ)-300 and ELQ-316 have been proven to be safe and efficacious against related apicomplexans, such as Plasmodium spp., with ELQ-316 also being effective against Babesia microti, without showing toxicity in mammals.
METHODS
The inhibitory effects of ELQ-300 and ELQ-316 were assessed on the growth of cultured B. bovis, B. bigemina, B. caballi and T. equi. The percentage of parasitized erythrocytes was measured by flow cytometry, and the effect of the ELQ compounds on the viability of horse and bovine peripheral blood mononuclear cells (PBMC) was assessed by monitoring cell metabolic activity using a colorimetric assay.
RESULTS
We calculated the half maximal inhibitory concentration (IC) at 72 h, which ranged from 0.04 to 0.37 nM for ELQ-300, and from 0.002 to 0.1 nM for ELQ-316 among all cultured parasites tested at 72 h. None of the parasites tested were able to replicate in cultures in the presence of ELQ-300 and ELQ-316 at the maximal inhibitory concentration (IC), which ranged from 1.3 to 5.7 nM for ELQ-300 and from 1.0 to 6.0 nM for ELQ-316 at 72 h. Neither ELQ-300 nor ELQ-316 altered the viability of equine and bovine PBMC at their IC in in vitro testing.
CONCLUSIONS
The compounds ELQ-300 and ELQ-316 showed significant inhibitory activity on the main parasites responsible for bovine babesiosis and equine piroplasmosis at doses that are tolerable to host cells. These ELQ drugs may be viable candidates for developing alternative protocols for the treatment of bovine babesiosis and equine piroplasmosis.
背景
引起牛巴贝斯虫病的最常见顶复门寄生虫是牛巴贝斯虫和双芽巴贝斯虫，而马巴贝斯虫和马媾疫锥虫则导致马梨形虫病。这些疾病的治疗和控制通常使用潜在有毒的化疗药物，如二丙氨嘧啶，但耐药寄生虫正在出现，需要替代有效且更安全的药物。内脂素样喹诺酮（ELQ）-300 和 ELQ-316 已被证明对相关顶复门寄生虫如疟原虫安全有效，ELQ-316 对微小巴贝斯虫也有效，且在哺乳动物中无毒性。
方法
评估 ELQ-300 和 ELQ-316 对培养的牛巴贝斯虫、双芽巴贝斯虫、马巴贝斯虫和马媾疫锥虫生长的抑制作用。通过流式细胞术测量寄生虫感染的红细胞百分比，并通过监测细胞代谢活性来评估 ELQ 化合物对马和牛外周血单核细胞（PBMC）活力的影响，使用比色法进行评估。
结果
我们计算了 72 小时的半最大抑制浓度（IC），ELQ-300 在 72 小时内对所有测试的培养寄生虫的 IC 范围为 0.04 至 0.37 nM，ELQ-316 的 IC 范围为 0.002 至 0.1 nM。在 ELQ-300 和 ELQ-316 的最大抑制浓度（IC）存在下，没有一种寄生虫能够在培养物中复制，ELQ-300 的 IC 范围为 1.3 至 5.7 nM，ELQ-316 的 IC 范围为 1.0 至 6.0 nM。在体外试验中，ELQ-300 和 ELQ-316 在其 IC 时均未改变马和牛 PBMC 的活力。
结论
化合物 ELQ-300 和 ELQ-316 在宿主细胞可耐受的剂量下对引起牛巴贝斯虫病和马梨形虫病的主要寄生虫表现出显著的抑制活性。这些 ELQ 药物可能是开发牛巴贝斯虫病和马梨形虫病替代治疗方案的可行候选药物。
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