Abstract：
Diminazene aceturate (DA), imidocarb dipropionate (ID), atovaquone (ATO), azithromycin (AZI), clindamycin, and quinine have been used to treat animal and human babesiosis for many years, despite their negative effects and rising indications of resistance. Thus, finding anti-babesial compounds that can either treat the infection or lower the dose of drugs given has been a primary objective. Quinazolines are one of the most important nitrogen heterocycles, with a wide range of pharmacological activities including analgesic, anti-inflammatory, sedative-hypnotic, anti-histaminic, anti-cancer, and anti-protozoan properties. The present study investigated the anti-babesial activities of twenty 6,7-dimethoxyquinazoline-2,4-diamines on Babesia spp. One candidate, 6,7-dimethoxy-N4-ethylisopropyl-N2-ethyl(pyridin-4-yl)quinazoline-2,4-diamine (SHG02), showed potent inhibition on Babesia gibsoni in vitro, as well as on B. microti and B. rodhaini in mice. Our findings indicate that the candidate compound SHG02 is promising for further development of anti-babesial drugs and provides a new structure to be explored for developing anti-Babesia therapeutics.
摘要：
二氮烯乙酸盐（DA），二丙酸亚胺酯(ID),atovaquone(ATO),阿奇霉素（AZI），克林霉素,和奎宁已经被用于治疗动物和人类的巴贝斯虫病很多年了，尽管他们的负面影响和不断上升的阻力迹象。因此，寻找可以治疗感染或降低给药剂量的抗babesial化合物是主要目标.喹唑啉是最重要的氮杂环化合物之一,具有广泛的药理活性，包括镇痛，抗炎,镇静催眠药,抗组胺,抗癌，和抗原生动物的特性。本研究调查了二十种6,7-二甲氧基喹唑啉-2,4-二胺对巴贝斯虫的抗巴贝斯活性。一个候选人,6,7-二甲氧基-N4-乙基异丙基-N2-乙基(吡啶-4-基)喹唑啉-2,4-二胺(SHG02)，在体外对gibsoni巴贝斯表现出有效的抑制作用，以及小鼠的B.microti和B.rodhaini。我们的发现表明候选化合物SHG02有望进一步开发抗巴贝斯虫药物，并为开发抗巴贝斯虫疗法提供了新的结构。
