Objective: To test the activity of aromatic pyrrole-based compounds against cercariae of Schistosoma japonicum and test their acute toxicity to fish.
Methods: A series of aromatic pyrrole-based compounds were synthesized using 4-benzyl-5-(trifluoromethyl)-1H-pyrrole-3-nitrile as the lead compound. The synthesized compounds were prepared into solutions at concentrations of 10.00, 1.00, 0.10, 0.01 mg/L, and the activity of these solutions against S. japonicum cercariae was tested in 30 min, while 0.10 mg/L and 0.01 mg/L niclosamide solutions served as a positive control and dechlorinated water with 1% dimethyl sulfoxide (DMSO) was used as a negative control, with 10 to 30 cercariae of S. japonicum in each group. In addition, the compounds were prepared into solutions at concentrations of 0.50, 0.25, 0.12, 0.06, 0.03 mg/L, and their toxicity to zebrafish was tested in 72 h, while 0.15 mg/L and 0.30 mg/L niclosamide solutions served as a positive control and dechlorinated water with 1% DMSO was used as a negative control, with 10 zebrafishes in each group.
Results: A total of 7 aromatic pyrrole-based compounds were successfully synthesized. Treatment with compounds 102, 104 and 106 at a concentration of 0.01 mg/L for 30 min killed all S. japonicum cercariae, and compounds 105 and 107 showed no activity against cercariae. No death of cercariae was found in the blank control group, while treatment with 0.10 mg/L niclosamide for 10 min caused a 100% mortality rate of S. japonicum cercariae and 0.01 mg/L niclosamide failed to kill S. japonicum cercariae. No zebrafish death was found 72 h post-treatment with compounds 101, 104 and 105 at a concentration of 0.03 mg/L, and exposure to compounds 102, 103 and 106 at a concentration of 0.03 mg/L for 12 h resulted in a 100% mortality rate of zebrafish. No zebrafish death occurred 72 h post-treatment with 0.50 mg/L Compound 104, and no zebrafish death was found in the blank control group, while treatment with 0.30 mg/L niclosamide for 24 h resulted in a 100% mortality rate of zebrafish.
Conclusions: Compound 104 achieves a 100% mortality rate against S. japonicum cercariae at a concentration of 0.01 mg/L for 30 min, and causes no death of zebrafish at a concentration of 0.50 mg/L for 72 h, which may serve as a cercaricide candidate.
［摘要］ 目的 探讨芳香吡咯类化合物杀灭日本血吸虫尾蚴活性及对鱼类的急性毒性。方法 以4-苄基-5-(三氟甲基)-1H-吡咯-3-腈为先导化学法合成并表征一系列芳香吡咯类化合物。将合成的化合物配制成10.00、1.00、0.10、0.01 mg/L浓度的药液作用于10~30条新鲜逸出的日本血吸虫尾蚴, 观察并分析其30 min内在各药液中存活情况; 以0.10、0.01 mg/L氯硝柳胺水溶液为阳性对照, 以含1%二甲基亚砜 (DMSO) 的脱氯水为空白对照。将10条斑马鱼暴露于浓度分别为0.50、0.25、0.12、0.06、0.03 mg/L的各化合物药液, 连续观察72 h斑马鱼在药液中的存活情况; 以0.15、0.30 mg/L 氯硝柳胺水溶液为阳性对照, 以含1% DMSO的脱氯水为空白对照。结果 成功合成7种芳香吡咯类化合物。0.01 mg/L 化合物102、104和106作用30 min均杀灭全部尾蚴, 化合物105和化合物107无杀蚴活性。空白对照组未见血吸虫尾蚴死亡; 0.10 mg/L氯硝柳胺处理10 min后尾蚴全部死亡, 但0.01 mg/L氯硝柳胺未能杀死血吸虫尾蚴。0.03 mg/L浓度化合物101、104和105处理72 h未导致斑马鱼死亡, 化合物102、103和106作用12 h可导致全部斑马鱼死亡。0.50 mg/L化合物104作用72 h未导致斑马鱼死亡, 空白对照组未见斑马鱼死亡, 0.30 mg/L氯硝柳胺处理24 h后斑马鱼全部死亡。结论 0.01 mg/L化合物104作用30 min可杀灭全部日本血吸虫尾蚴, 0.50 mg/L作用72 h未导致斑马鱼死亡, 可以作为杀蚴剂候选化合物。.
Keywords:
Acute toxicity; Aromatic pyrrole-based compound; Cercaricidal activity;