G Silva Marta, Knowles Donald P, Antunes Sandra, Domingos Ana, Esteves Maria A, Suarez Carlos E
Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA 99164-7040, USA.
Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA 99164-7040, USA; Animal Disease Research Unit, USDA-ARS, 3003 ADBF, WSU, Pullman, WA, 99163-6630, USA.
Ticks Tick Borne Dis. 2017 Jun;8(4):593-597. doi: 10.1016/j.ttbdis.2017.04.002. Epub 2017 Apr 10.
Bovine and equine babesiosis caused by Babesia bovis, Babesia bigemina and Babesia caballi, along with equine theileriosis caused by Theileria equi are global tick-borne hemoprotozoan diseases characterized by fever, anemia, weight losses and abortions. A common feature of these diseases are transition from acute to chronic phases, in which parasites may persist in the hosts for life. Antiprotozoal drugs are important for managing infection and disease. Previous research demonstrated that trifluralin analogues, designated (TFLAs) 1-15, which specifically bind to regions of alpha-tubulin protein in plants and protozoan parasites, have the ability to inhibit the in vitro growth of B. bovis. The inhibitory activity of TFLAs 1-15 minus TFLA 5 was tested in vitro against cultured B. bigemina, B. caballi and T. equi. The four TFLAs with greatest inhibitory activity were then analyzed for hemolytic activity and toxicity against erythrocytes. All TFLAs tested in the study showed inhibitory effects against the three parasite species. TFLA 2, TFLA 11, TFLA 13 and TFLA 14 were the most effective inhibitors for the three species tested, with estimated IC between 5.1 and 10.1μM at 72h. The drug's solvent (DMSO/ethanol) did not statistically affect the growth of the parasites nor cause hemolysis. Also, TFLA 2, 13 and 14 did not cause statistically significant hemolytic activity on bovine and equine erythrocytes at 15μM, and TFLA 2, 11 and 13 had no detectable toxic effects on bovine and equine erythrocytes at 15μM, suggesting that these drugs do not compromise erythrocyte viability. The demonstrated ability of the trifluralin analogues to inhibit in vitro growth of Babesia spp. and Theileria equi, and their lack of toxic effects on erythrocytes supports further in vivo testing and eventually their development as novel alternatives for the treatment of babesiosis and theileriosis.
由牛巴贝斯虫、双芽巴贝斯虫和马巴贝斯虫引起的牛和马巴贝斯虫病，以及由驽巴贝斯虫引起的马泰勒虫病，是全球蜱传血液原虫病，其特征为发热、贫血、体重减轻和流产。这些疾病的一个共同特征是从急性期过渡到慢性期，在此期间寄生虫可能在宿主体内终生存在。抗原虫药物对于控制感染和疾病很重要。先前的研究表明，氟乐灵类似物（命名为TFLAs 1-15）能特异性结合植物和原生动物寄生虫中α-微管蛋白的区域，具有抑制牛巴贝斯虫体外生长的能力。测试了TFLAs 1-15（减去TFLA 5）对培养的双芽巴贝斯虫、马巴贝斯虫和驽巴贝斯虫的体外抑制活性。然后分析了具有最大抑制活性的四种TFLAs对红细胞的溶血活性和毒性。研究中测试的所有TFLAs均显示出对这三种寄生虫的抑制作用。TFLA 2、TFLA 11、TFLA 13和TFLA 14是测试的三种寄生虫最有效的抑制剂，在72小时时估计IC50在5.1至10.1μM之间。药物的溶剂（二甲基亚砜/乙醇）对寄生虫的生长没有统计学上的影响，也不会引起溶血。此外，TFLA 2、13和14在15μM时对牛和马红细胞没有统计学上显著的溶血活性，TFLA 2、11和13在15μM时对牛和马红细胞没有可检测到的毒性作用，这表明这些药物不会损害红细胞的活力。氟乐灵类似物在体外抑制巴贝斯虫属和驽巴贝斯虫生长的能力，以及它们对红细胞缺乏毒性作用，支持进一步进行体内测试，并最终将它们开发为治疗巴贝斯虫病和泰勒虫病的新型替代药物。
