Faculdade de Farmácia, Departamento de Ciências Farmacêuticas, Universidade Federal de Juiz de Fora, R. José Lourenço Kelmer s/n, Campus Universitário, Juiz de Fora, MG, 36036-900, Brazil.
Departamento de Química, Universidade Federal de Juiz de Fora, Juiz de Fora, MG, 36036-900, Brazil.
Acta Trop. 2021 Jan;213:105741. doi: 10.1016/j.actatropica.2020.105741. Epub 2020 Nov 5.
Schistosomiasis is a neglected disease caused by helminth flatworms of the genus Schistosoma, affecting over 240 million people in more than 70 countries. The treatment relies on a single drug, praziquantel, making urgent the discovery of new compounds. Aurones are a natural type of flavonoids that display interesting pharmacological activities, particularly as chemotherapeutic agents against parasites. In pursuit of treatment alternatives, the present work conducted an in vitro and in vivo antischistosomal investigation with aurone derivatives against Schistosoma mansoni. After preparation of aurone derivatives and their in vitro evaluation on adult schistosomes, the three most active aurones were evaluated in cytotoxicity and haemolytic assays, as well as in confocal laser-scanning microscope studies, showing tegumental damage in parasites in a concentration-dependent manner with no haemolytic or cytotoxic potential toward mammalian cells. In a mouse model of schistosomiasis, at a single oral dose of 400 mg/kg, the selected aurones showed worm burden reductions of 35% to 65.0% and egg reductions of 25% to 70.0%. The most active thiophenyl aurone derivative 18, unlike PZQ, had efficacy in mice harboring juvenile S. mansoni, also showing significant inhibition of oviposition by parasites, giving support for the antiparasitic potential of aurones as lead compounds for novel antischistosomal drugs.
血吸虫病是一种由血吸虫属的扁形动物引起的被忽视的疾病，影响了 70 多个国家的超过 2.4 亿人。这种疾病的治疗依赖于一种单一的药物，即吡喹酮，因此迫切需要发现新的化合物。奥罗内是一种天然的类黄酮，具有有趣的药理活性，特别是作为抗寄生虫的化疗药物。为了寻找治疗替代方法，本工作对奥罗内衍生物对曼氏血吸虫的体外和体内抗血吸虫作用进行了研究。在制备奥罗内衍生物并对其进行体外评估后，对三种最活跃的奥罗内衍生物进行了细胞毒性和溶血试验以及共聚焦激光扫描显微镜研究，结果显示，这些奥罗内衍生物以浓度依赖的方式对寄生虫的表皮造成损伤，对哺乳动物细胞没有溶血或细胞毒性。在曼氏血吸虫病的小鼠模型中，单一口服剂量为 400mg/kg 时，所选奥罗内衍生物对成虫的减虫率为 35%至 65.0%，对虫卵的减卵率为 25%至 70.0%。与 PZQ 不同，最活跃的噻吩奥罗内衍生物 18 对携带曼氏血吸虫幼虫的小鼠也有效，同时也显示出对寄生虫产卵的显著抑制作用，这为奥罗内作为新型抗血吸虫药物的先导化合物的抗寄生虫潜力提供了支持。
