National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Inada-cho, Obihiro, Hokkaido 080-8555, Japan; Department of Internal Medicine and Infectious Diseases, Faculty of Veterinary Medicine, Mansoura University, Mansoura 35516, Egypt.
National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Inada-cho, Obihiro, Hokkaido 080-8555, Japan; Department of Biochemistry and Chemistry of Nutrition, Faculty of Veterinary Medicine, Mansoura University, Mansoura 35516, Egypt.
Vet Parasitol. 2019 Oct;274:108895. doi: 10.1016/j.vetpar.2019.07.003. Epub 2019 Jul 19.
There is an innovative approach to discovering and developing novel potent and safe anti-Babesia and anti-Theileria agents for the control of animal piroplasmosis. Large-scale screening of 400 compounds from a Malaria Box (a treasure trove of 400 diverse compounds with antimalarial activity has been established by Medicines for Malaria Venture) against the in vitro growth of bovine Babesia and equine Babesia and Theileria parasites was performed, and the data were published in a brief with complete dataset from 236 screens of the Malaria Box compounds. Therefore, in this review, we explored and discussed in detail the in vitro inhibitory effects of 400 antimalarial compounds (200 drug-like and 200 probe-like) from the Malaria Box against Babesia (B.) bovis, B. bigemina, B. caballi, and Theileria (T.) equi. Seventeen hits were the most interesting with regard to bovine Babesia parasites, with mean selectivity indices (SIs) greater than 300 and half maximal inhibitory concentration (ICs) ranging from 50 to 410 nM. The most interesting compounds with regard to equine Babesia and Theileria parasites were MMV020490 and MMV020275, with mean SIs > 258.68 and >251.55, respectively, and ICs ranging from 76 to 480 nM. Ten novel anti-B. bovis, anti-B. bigemina, anti-T. equi, and anti-B. caballi hits, MMV666093, MMV396794, MMV006706, MMV665941, MMV085203, MMV396693, MMV006787, MMV073843, MMV007092, and MMV665875, with nanomole levels of IC were identified. The most interesting hits were MMV396693, MMV073843, MMV666093, and MMV665875, with mean SIs greater than 307.8 and ICs ranging from 43 to 630 nM for both bovine Babesia and equine Babesia and Theileria parasites. Screening the Malaria Box against the in vitro growth of Babesia and Theileria parasites helped with the discovery of new drugs than those traditionally used, diminazene aceturate and imidocarb dipropionate, and indicated the potential of the Malaria Box in finding new, potent antibabesial drugs.
有一种创新的方法可以发现和开发新型强效且安全的抗巴贝斯虫和泰勒虫药物，用于控制动物巴贝斯虫病。对疟疾药箱（由疟疾风险药物基金会建立的 400 种具有抗疟活性的多样化化合物的宝库）中的 400 种化合物进行了大规模筛选，以检测其对牛巴贝斯虫和马巴贝斯虫及泰勒虫寄生虫的体外生长的抑制作用，并在一份简短的报告中公布了来自疟疾药箱 236 次筛选的完整数据集。因此，在本综述中，我们详细探讨和讨论了疟疾药箱中的 400 种抗疟化合物（200 种类似药物和 200 种探针样化合物）对牛巴贝斯虫（B. bovis）、双芽巴贝斯虫（B. bigemina）、马巴贝斯虫（B. caballi）和泰勒虫（T. equi）的体外抑制作用。在牛巴贝斯虫寄生虫方面，有 17 个化合物是最有趣的，它们的平均选择性指数（SI）大于 300，半数最大抑制浓度（IC）范围为 50 至 410 nM。在马巴贝斯虫和泰勒虫寄生虫方面，最有趣的化合物是 MMV020490 和 MMV020275，其平均 SI 分别大于 258.68 和 251.55，IC 范围为 76 至 480 nM。鉴定出了 10 种新型抗牛巴贝斯虫、抗马巴贝斯虫、抗泰勒虫和抗马巴贝斯虫的化合物，分别是 MMV666093、MMV396794、MMV006706、MMV665941、MMV085203、MMV396693、MMV006787、MMV073843、MMV007092 和 MMV665875，它们的 IC 值为纳摩尔级。最有趣的化合物是 MMV396693、MMV073843、MMV666093 和 MMV665875，它们对牛巴贝斯虫和马巴贝斯虫寄生虫的平均 SI 大于 307.8，IC 范围为 43 至 630 nM。对疟疾药箱进行抗巴贝斯虫和泰勒虫寄生虫的体外生长筛选有助于发现比传统使用的药物，如二脒那嗪和咪唑苯脲，更有效的新药，并表明疟疾药箱在寻找新型强效抗巴贝斯虫药物方面具有潜力。
