A previous phenotypic screening campaign led to the identification of a quinazoline derivative with promising in vitro activity against Schistosoma mansoni. Follow-up studies of the antischistosomal potential of this candidate are presented here. The in vivo studies in a S. mansoni mouse model show a significant reduction of total worms and a complete disappearance of immature eggs when administered concomitantly with praziquantel in comparison with the administration of praziquantel alone. This fact is of utmost importance because eggs are responsible for the pathology and transmission of the disease. Subsequently, the chemical optimisation of the structure in order to improve the metabolic stability of the parent compound was carried out leading to derivatives with improved drug-like properties. Additionally, the putative target of this new class of antischistosomal compounds was envisaged by using computational tools and the binding mode to the target enzyme, aldose reductase, was proposed.

中文翻译：

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使用补充的计算工具，对带有喹唑啉支架的抗血吸虫新药家族的酶促目标进行破译。

先前的表型筛选活动导致鉴定出具有对曼氏血吸虫有希望的体外活性的喹唑啉衍生物。此处介绍了该候选人的抗血吸虫病潜力的后续研究。在曼氏葡萄球菌小鼠模型中的体内研究显示，与单独使用吡喹酮相比，与吡喹酮合用时，蠕虫总数明显减少，未成熟卵完全消失。这个事实至关重要，因为鸡蛋是造成该疾病的病理和传播原因。随后，为了改善母体化合物的代谢稳定性，进行了结构的化学优化，从而得到了具有改善的类药物性质的衍生物。另外，