Babesiosis is an infectious disease with an empty drug pipeline. A search inside chemical libraries for novel potent antibabesial candidates may help fill such an empty drug pipeline. A total of 400 compounds (200 drug-like and 200 probe-like) from the Malaria Box were evaluated in the current study against the in vitro growth of Babesia divergens (B. divergens), a parasite of veterinary and zoonotic importance. Novel and more effective anti-B. divergens drugs than the traditionally used ones were identified. Seven compounds (four drug-like and three probe-like) revealed a highly inhibitory effect against the in vitro growth of B. divergens, with IC₅₀s ≤ 10 nanomolar. Among these hits, MMV006913 exhibited an IC₅₀ value of 1 nM IC₅₀ and the highest selectivity index of 32,000. The atom pair fingerprint (APfp) analysis revealed that MMV006913 and MMV019124 showed maximum structural similarity (MSS) with atovaquone and diminazene aceturate (DA), and with DA and imidocarb dipropionate (ID), respectively. MMV665807 and MMV665850 showed MMS with each other and with ID. Of note, a high concentration (0.75 IC₅₀) of MMV006913 caused additive inhibition of B. divergens growth when combined with DA at 0.75 or 0.50 IC₅₀. The Medicines for Malaria Venture box is a treasure trove of anti-B. divergens candidates according to the obtained results.

中文翻译：

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疟疾风险药物中的化合物抑制巴贝虫的体外生长，这是一种具有兽医和人畜共患重要性的血源性寄生虫

巴贝虫病是一种药物管道空洞的传染病。在化学库中搜索新的强效抗巴贝斯候选药物可能有助于填补这样一个空白的药物管道。在目前的研究中，对来自疟疾盒的 400 种化合物（200 种药物样化合物和 200 种探针样化合物）进行了评估，以对抗巴贝虫（B.diversity ）的体外生长，这是一种具有兽医和人畜共患重要性的寄生虫。鉴定出比传统使用的更新颖和更有效的抗B.differs药物。七种化合物（四种药物样化合物和三种探针样化合物）显示出对B.differns体外生长的高度抑制作用，IC ₅₀s ≤ 10 纳摩尔。在这些命中中，MMV006913 显示出1 nM IC _{50的 IC 50}值和 32,000 的最高选择性指数。原子对指纹 (APfp) 分析表明，MMV006913 和 MMV019124 分别与 atovaquone 和醋酸二亚胺 (DA) 以及 DA 和二丙酸咪唑威 (ID) 显示出最大的结构相似性 (MSS)。MMV665807 和 MMV665850 显示 MMS 彼此并带有 ID。值得注意的是，当与 0.75 或 0.50 IC _{50的 DA 组合时，高浓度 (0.75 IC 50 ) 的 MMV006913 引起了对}B.diversity生长的加性抑制。疟疾药物风险投资箱是抗B. 分歧的宝库候选人根据获得的结果。