Browsing by Author "Silva, Milene Lopes da"
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Item In vitro tripanocidal effect of 1,8-dioxooctahydroxanthenes (xanthenodiones) and tetraketones and improvement of cardiac parameters in vivo.(2020) Menezes, Ana Paula de Jesus; Silva, Milene Lopes da; Pereira, Wagner Luiz; Costa, Guilherme de Paula; Horta, Aline Luciano; Mendonça, Andréa Aparecida dos Santos; Carneiro, Ana Cláudia Alvarenga; Souza, Débora Maria Soares de; Novaes, Rômulo Dias; Teixeira, Róbson Ricardo; Silva, André Talvani Pedrosa daObjective: Trypanosoma cruzi infection affects millions of people worldwide, and the drugs available for its treatment have limited efficacy. 1,8-Dioxooctahydroxanthenes and tetraketones are compounds with important biological applications. The aim of this study was to assess the trypanocidal and inflammatory activities of nine 1,8-dioxooctahydroxanthenes (1–9) and three tetraketones (10–12). Methods and results: By in vitro killing assay, three compounds were able to eliminate CL TdTomato expressing strain of T. cruzi, 9 (IC50 = 30.65mM), 10 (IC50 = 14.11mM), and 11 (IC50 = 26.43mM). However, only 9 was not toxic to Vero cells. Next, to evaluate the in vivo antitrypanosomal and immunological efficacy of 9, Swiss mice were infected with the Y and CL strains of T. cruzi and treated for 10 days with 50 mg/kg of 9. This compound reduced the cardiac inflammatory infiltration in animals infected with both strains. Rank's ligand (RankL), CCL2, and interferon (IFN)-g were measured in the cardiac tissue homogenate of the Y-strain-infected animals, and no interference of 9 was observed. However, compound 9 increased the RankL and interleukin (IL)-10 levels in CL-infected mice. No hepatic and renal toxicity was observed. Conclusion: Our findings showed that 1,8-dioxooctahydroxanthene has antiparasitic effect and ameliorates the cardiac inflammatory parameters related to T. cruzi infection.