Centre for Respiratory Biology, UCL Respiratory, Division of Medicine, University College London, London, United Kingdom.
Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom.
PLoS Negl Trop Dis. 2018 Jul 11;12(7):e0006487. doi: 10.1371/journal.pntd.0006487. eCollection 2018 Jul.
The human whipworm Trichuris trichiura is 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 parasite in 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.
人体鞭虫 Trichuris trichiura 是一种寄生虫，全球约有 5 亿人感染，其后果包括身体生长和教育表现受损。与其他土壤传播的蠕虫相比，当前的药物如甲苯咪唑对鞭虫的疗效明显不足。因此，大规模药物管理计划不太可能实现根除，迫切需要新的鞭虫病治疗方法。所有当前的药物控制策略都集中在感染后的根除上，针对体内寄生虫。在这里，我们建议开发针对土壤中寄生虫卵期的新型驱虫药，作为一种辅助环境策略。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，即 2,4-二氨基噻吩并[3,2-d]嘧啶（DATPs）。该化合物类别在药物化学中具有广泛的用途，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年寄生虫有效，而且对胚胎和非胚胎卵期都有效，从而可能打破寄生虫的生命周期。
