DEFAR - Artigos publicados em periódicos
URI permanente para esta coleçãohttp://www.hml.repositorio.ufop.br/handle/123456789/531
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Item In vitro and in silico evaluation of the schistosomicidal activity of eugenol derivatives using biochemical, molecular, and morphological tools.(2022) Souza, Isabella Maria Monteiro de; Novaes, Rômulo Dias; Gonçalves, Reggiani Vilela; Fialho, Felipe Leonardo Bley; Carvalho, Diogo Teixeira; Souza, Thiago Belarmino de; Dias, Danielle Ferreira; Lavorato, Stefânia Neiva; Souza, Raquel Lopes Martins; Marques, Marcos José; Castro, Aline PereiraBackground: 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.Item Synthesis, trypanocidal and cytotoxic activities of α,β-unsaturated ketones derived from eugenol and analogues.(2022) Reis, Rúbia Castro Fernandes Melo; Reis, Adriana Cotta Cardoso; Torchelsen, Fernanda Karoline Vieira da Silva; Lana, Marta de; Sales Júnior, Policarpo Ademar; Brandão, Geraldo Célio; Braga, Saulo Fehelberg Pinto; Souza, Thiago Belarmino deThis work describes the synthesis, structural characterization, trypanocide and cytotoxic evaluation of α,β-unsaturated ketones derived from eugenol and analogues. Among the synthesized compounds, the cyclopentanonic/dihydroeugenol derivative 12 was active against amastigote forms of Trypanosoma cruzi at 5.2 nM (700 times more potent than benznidazole) and represents a potential hit for future structural optimizations to reduce its toxicity. All the compounds were also evaluated against a healthy human and four cancer cell lines and the derivative 10 was more active than doxorubicin against three cancer cells (IC50 values between 2.03–23.51 μM) and showed the higher selectivity index considering the human cells. Derivative 14 was also more potent and selective than doxorubicin against two cancer cells (IC50 values between 4.71–8.86 μM).Item Synthesis, activity, and molecular modeling studies of 1,2,3‐ triazole derivatives from natural phenylpropanoids as new trypanocidal agents.(2019) Souza, Thiago Belarmino de; Caldas, Ivo Santana; Paula, Favero Reisdorfer; Rodrigues, Camila Coelho; Carvalho, Diogo Teixeira; Dias, Danielle FerreiraThe search for compounds with new structural scaffolds is an important tool to the discovery of new drugs against Chagas disease. We report herein the synthesis of 1,2,3‐triazoles obtained from eugenol and di‐hydroeugenol and their in vitro and in vivo trypanocidal activity. These derivatives were obtained by a three‐step objective route and were suitably characterized by 1H and 13C nuclear magnetic resonance spectroscopy and high‐resolution mass spectrometry. Two compounds (9 and 10 ) showed activity against epimastigote forms of Trypanosoma cruzi (Y strain) in the range 42.8–88.4 μM and were weakly toxic to cardiomyoblast cells (H9c2 cells). The triazole 10 was the most active derivative and could reduce more than 50% of parasitemia after a 100‐mg/kg oral treatment of mice infected with T. cruzi . Molecular docking studies suggested this compound could act as a trypanocidal agent by inhibiting cruzain, an essential enzyme for T. cruzi metabolism, usually inhibited by triazole compounds.