对曼氏血吸虫幼虫具有活性的吡喹酮类似物。
Praziquantel analogs with activity against juvenile Schistosoma mansoni.
作者信息
Dong Yuxiang, Chollet Jacques, Vargas Mireille, Mansour Nuha R, Bickle Quentin, Alnouti Yazen, Huang Jiangeng, Keiser Jennifer, Vennerstrom Jonathan L
机构信息
University of Nebraska Medical Center, College of Pharmacy, Omaha, NE, USA.
出版信息
Bioorg Med Chem Lett. 2010 Apr 15;20(8):2481-4. doi: 10.1016/j.bmcl.2010.03.001. Epub 2010 Mar 4.
Six amide and four urea derivatives of praziquantel were synthesized and tested for antischistosomal activity against juvenile and adults stages of Schistosoma mansoni in infected mice. Only one of these had significant activity against adult worms, but, unlike praziquantel, six of these had low to modest activity against juvenile worms. A praziquantel ketone derivative had the best combination of activity against juveniles and adults, but it had no effect on the motility of adult S. mansoni in ex vivo culture. Cytochrome P450 metabolic stability data support the hypothesis that the major trans-cyclohexanol metabolite of praziquantel plays an important role in the antischistosomal activity of this drug.
合成了吡喹酮的六种酰胺衍生物和四种脲衍生物，并在感染曼氏血吸虫的小鼠体内对其针对曼氏血吸虫幼虫和成虫阶段的抗血吸虫活性进行了测试。其中只有一种对成虫具有显著活性，但与吡喹酮不同的是，其中六种对幼虫具有低至中等活性。一种吡喹酮酮衍生物在针对幼虫和成虫的活性方面具有最佳组合，但它对离体培养的曼氏血吸虫成虫的活力没有影响。细胞色素P450代谢稳定性数据支持这样的假设，即吡喹酮的主要反式环己醇代谢物在该药物的抗血吸虫活性中起重要作用。
Zotero 插件