Souza, Isabella Maria Monteiro deNovaes, Rômulo DiasGonçalves, Reggiani VilelaFialho, Felipe Leonardo BleyCarvalho, Diogo TeixeiraSouza, Thiago Belarmino deDias, Danielle FerreiraLavorato, Stefânia NeivaSouza, Raquel Lopes MartinsMarques, Marcos JoséCastro, Aline Pereira2023-10-182023-10-182022SOUZA, I. M. M. de et al. In vitro and in silico evaluation of the schistosomicidal activity of eugenol derivatives using biochemical, molecular, and morphological tools. Journal of Venomous Animals and Toxins Including Tropical Diseases, v. 28, artigo e20210108, 2022. Disponível em: <https://www.scielo.br/j/jvatitd/a/m5FQpQLh53JqVTxdss3Kn4v/abstract/?lang=en>. Acesso em: 01 ago. 2023.1678-9199http://www.repositorio.ufop.br/jspui/handle/123456789/17598Background: 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 in vitro activities of three eugenol derivatives (FB1, FB4 and FB9) on adult worms from Schistosoma mansoni 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 in silico analysis identified potential Na+/K+-ATPase binding sites. Results: The compounds showed effective doses (ED50) of 0.324 mM (FB1), 0.167 mM (FB4), and 0.340 mM (FB9). In addition, FB4 (0.322 mM), which showed the lowest ED50, ED90 and ED100 (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 versus 72 hours) and FB9 (192 versus 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 in silico 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 S. mansoni worms.en-USabertoSchistosoma mansoniEugenolSchistosomiasisMechanism of actionArtigo publicado em periodicoThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http:// creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. Fonte: PDF do artigo.https://doi.org/10.1590/1678-9199-JVATITD-2021-0108