2,4-Diaminothieno[3,2- d ]pyrimidines, a new class of anthelmintic with activity against adult and egg stages of whipworm
2,4-Diaminothieno[3,2- d ]pyrimidines, a new class of anthelmintic with activity against adult and egg stages of whipworm
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2,4-二氨基噻吩并[3,2-d]嘧啶，一类新型驱虫药，具有对抗鞭虫成虫和卵阶段的活性
DOI：
10.1101/254037
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Partridge F
中科院分区：
文献类型：
--
作者：
Partridge F
人类鞭虫鞭虫是一种寄生虫，感染了全球约5亿人，其后果包括损害身体发育和教育成绩。与其他土壤传播的蠕虫相比，目前的药物如甲苯咪唑对鞭虫缺乏明显的疗效。因此，大规模药物管理项目不太可能实现根除，迫切需要治疗鞭毛虫病的新方法。目前所有的药物控制策略都侧重于感染后根除，以体内寄生虫为靶标。在这里，我们建议开发新的驱虫剂，以土壤中寄生虫的卵期为目标，作为一种辅助的环境策略。作为支持这种方法的证据，我们描述了一类新的驱虫化合物，2，4-二氨基硫代并[3，2-d]嘧啶(DATPs)的作用。这类化合物在药物化学中发现了广泛的用途，但以前没有被描述为具有驱虫活性。重要的是，这些化合物不仅对成虫有效，而且对胚胎阶段和非胚胎阶段都有效，从而可能打破寄生虫的生命周期。
The human whipwormTrichuris trichiurais a parasite that infects around 500 million people globally, with consequences including damage to physical growth and educational performance. Current drugs such as mebendazole have a notable lack of efficacy against whipworm, compared to other soil-transmitted helminths. Mass drug administration programs are therefore unlikely to achieve eradication and new treatments for trichuriasis are desperately needed. All current drug control strategies focus on post-infection eradication, targeting the parasitein vivo. Here we propose developing novel anthelmintics which target the egg stage of the parasite in the soil as an adjunct environmental strategy. As evidence in support of such an approach we describe the actions of a new class of anthelmintic compounds, the 2,4-diaminothieno[3,2-d]pyrimidines (DATPs). This compound class has found broad utility in medicinal chemistry, but has not previously been described as having anthelmintic activity. Importantly, these compounds show efficacy against not only the adult parasite, but also both the embryonated and unembryonated egg stages and thereby may enable a break in the parasite lifecycle.