以及使用生化、分子和形态学工具对丁香酚衍生物的杀血吸虫活性进行评估。
and evaluation of the schistosomicidal activity of eugenol derivatives using biochemical, molecular, and morphological tools.
作者信息
de Souza Isabella Maria Monteiro, Novaes Romulo Dias, Gonçalves Reggiani Vilela, Fialho Felipe Leonardo Bley, Carvalho Diogo Teixeira, de Souza Thiago Belarmino, Dias Danielle Ferreira, Lavorato Stefânia Neiva, Souza Raquel Lopes Martins, Marques Marcos José, Castro Aline Pereira
机构信息
Institute of Biomedical Sciences, Federal University of Alfenas (Unifal), Alfenas, MG, Brazil.
Department of Animal Biology, Federal University of Viçosa, Viçosa, MG, Brazil.
出版信息
J Venom Anim Toxins Incl Trop Dis. 2022 Jul 1;28:e20210108. doi: 10.1590/1678-9199-JVATITD-2021-0108. eCollection 2022.
BACKGROUND
Eugenol shows both antibacterial and antiparasitic activities, suggesting that it might be evaluated as an option for the treatment of praziquantel-resistant schistosome.
METHODS
The activities of three eugenol derivatives (FB1, FB4 and FB9) on adult worms from were examined by fluorescence and scanning electron microscopy to analyze effects on the excretory system and integument damage, respectively. Biochemical tests with verapamil (a calcium channel antagonist) and ouabain (a Na/K-ATPase pump inhibitor) were used to characterize eugenol derivative interactions with calcium channels and the Na/K-ATPase, while analysis identified potential Na/K-ATPase binding sites.
RESULTS
The compounds showed effective doses (ED) of 0.324 mM (FB1), 0.167 mM (FB4), and 0.340 mM (FB9). In addition, FB4 (0.322 mM), which showed the lowest ED ED and ED (p < 0.05), caused the most damage to the excretory system and integument, according to both fluorescence and scanning electron microscopy analysis. The death of adult worms was delayed by ouabain treatment plus FB1 (192 72 hours) and FB9 (192 168 hours), but the response to FB4 was the same in the presence or absence of ouabain. Besides, no changes were noted when all of the eugenol derivatives were combined with verapamil. Moreover, FB1 and FB9 inhibited Na/K-ATPase activity according to analysis but FB4 did not show a time-dependent relationship and may act on targets other than the parasite Na+/K+-ATPase.
CONCLUSION
Eugenol derivatives, mainly FB4 when compared to FB1 and FB9, seem to act more effectively on the integument of adult worms.
背景
丁香酚具有抗菌和抗寄生虫活性，这表明它可能被评估为治疗对吡喹酮耐药的血吸虫的一种选择。
方法
通过荧光显微镜和扫描电子显微镜分别检测三种丁香酚衍生物（FB1、FB4和FB9）对成虫的活性，以分析其对排泄系统的影响和体表损伤情况。使用维拉帕米（一种钙通道拮抗剂）和哇巴因（一种钠钾ATP酶泵抑制剂）进行生化试验，以表征丁香酚衍生物与钙通道和钠钾ATP酶的相互作用，同时进行分析以确定潜在的钠钾ATP酶结合位点。
结果
这些化合物的有效剂量（ED）分别为0.324 mM（FB1）、0.167 mM（FB4）和0.340 mM（FB9）。此外，根据荧光显微镜和扫描电子显微镜分析，ED最低的FB4（0.322 mM）对排泄系统和体表造成的损伤最大。哇巴因处理加FB1（192±72小时）和FB9（192±168小时）可延迟成虫死亡，但无论有无哇巴因，FB4的反应相同。此外，当所有丁香酚衍生物与维拉帕米联合使用时，未观察到变化。此外，根据分析，FB1和FB9抑制钠钾ATP酶活性，但FB4未显示出时间依赖性关系，可能作用于寄生虫钠钾ATP酶以外的靶点。
结论
与FB1和FB9相比，丁香酚衍生物，主要是FB4，似乎对成虫体表的作用更有效。
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