Praziquantel analogs with activity against juvenile Schistosoma mansoni
Praziquantel analogs with activity against juvenile Schistosoma mansoni
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DOI：
10.1016/j.bmcl.2010.03.001
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发表时间：
2010-04-15
影响因子：
2.7
通讯作者：
Vennerstrom, Jonathan L.
中科院分区：
文献类型：
--
作者：
Dong, Yuxiang;Chollet, Jacques;Vennerstrom, Jonathan L.
合成了吡喹酮的六种酰胺和四种脲衍生物，并测试了对受感染小鼠曼氏血吸虫幼年期和成虫期的抗血吸虫活性。其中只有一种对成虫具有显着活性，但与吡喹酮不同，其中六种对幼虫具有低至中等活性。吡喹酮酮衍生物对幼虫和成虫具有最佳的活性组合，但对离体培养的曼氏链霉菌成虫的运动没有影响。细胞色素 P450 代谢稳定性数据支持这样的假设：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发挥重要作用。 (C) 2010 Elsevier Ltd. 保留所有权利。
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. (C) 2010 Elsevier Ltd. All rights reserved.