Schistosomiasis is a neglected tropical disease mainly affecting the poorest tropical and subtropical areas of the world with the impressive number of roughly 200 million infections per year. Schistosomes are blood trematode flukes of the genus Schistosoma causing symptoms in humans and animals. Organ morbidity is caused by the accumulation of parasite eggs and subsequent development of fibrosis. If left untreated, schistosomiasis can result in substantial morbidity and even mortality. Praziquantel (PZQ) is the most effective and widely used compound for the treatment of the disease, in prevention and control programs in the last 30 years. Unfortunately, it has no effect on juvenile immature schistosomes and cannot prevent reinfection or interfere with the schistosome life cycle; moreover drug-resistance represents a serious threat. The search for an alternative or complementary treatment is urgent and drug repurposing could accelerate a solution. The anti-anginal drug perhexiline maleate (PHX) has been previously shown to be effective on larval, juvenile, and adult stages of S. mansoni and to impact egg production in vitro. Since PHX is a racemic mixture of R-(+)- and S-(−)-enantiomers, we designed and realized a stereoselective synthesis of both PHX enantiomers and developed an analytical procedure for the direct quantification of the enantiomeric excess also suitable for semipreparative separation of PHX enantiomers. We next investigated the impact of each enantiomer on viability of newly transformed schistosomula (NTS) and worm pairs of S. mansoni as well as on egg production and vitellarium morphology by in vitro studies. Our results indicate that the R-(+)-PHX is mainly driving the anti-schistosomal activity but that also the S-(−)-PHX possesses a significant activity towards S. mansoni in vitro.

血吸虫病是一种被忽视的热带病，主要影响世界上最贫穷的热带和亚热带地区，每年感染人数约为2亿。血吸虫是血吸虫属的血吸虫性吸虫导致人类和动物出现症状。器官发病是由寄生虫卵的积累和随后的纤维化发展引起的。如果不加以治疗，血吸虫病可导致大量发病，甚至死亡。在过去30年的预防和控制计划中，吡喹酮（PZQ）是最有效和广泛使用的用于治疗该疾病的化合物。不幸的是，它对未成熟的儿童血吸虫没有影响，并且不能防止再感染或干扰血吸虫的生命周期。此外，耐药性是一个严重的威胁。寻找替代或补充治疗的迫切性和药物用途可以加速解决方案。先前已证明抗心绞痛药物马来酸哌己昔林（PHX）可有效治疗幼年期，幼年期和成年期的S. mansoni并影响体外产卵。由于PHX是R -（+）-和S -（-）-对映体的外消旋混合物，因此我们设计并实现了两种PHX对映体的立体选择性合成，并开发了直接定量对映体过量也适用于半制备的分析方法PHX对映体的分离。接下来，我们通过体外研究调查了每种对映异构体对新转化的血吸虫（NTS）和曼氏沙门氏菌蠕虫对的活力以及对产卵和vi的形态的影响。我们的结果表明，R -（+）-PHX主要驱动抗血吸虫活性，但是S -（-）-PHX在体外对曼氏链球菌具有显着的活性。