Journal des médicaments en développement
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Anti-Parasite effects of new Thiosemicarbazones and their Products Thiazolidinone including Cellular aspects of Intracellular Elimination of Trypanosoma Cruzi in Vitro

Laís P de Carvalho, Marco A G B Gomes, Barbara S Rocha, Rodrigo R de Oliveira, Edmilson J Maria and Edésio J T de Melo

Trypanosoma cruzi, agent of Chagas disease in humans, invades and replicates within a wide variety of nucleated mammalian cells until the lysis of the host cells. This study was undertaken to evaluate the cellular features of effect of new compounds of thiosemicarbazone and their thiazolidinone derivate on the multiplication of extra- and intracellular T. cruzi. Most of the compounds interrupted epimastigote proliferation at 1 mM, and above 5 mM led to drastic cytoplasm reduction, nuclear condensation and death. Ultrastructural assays showed that epimastigotes treated with 1 mM of the compounds retained main parasite organelles such as the Golgi complex and the mitochondria, but underwent drastic reduction in cytoplasm volume and led to the formation of blebs on the plasma membrane, suggesting a cell death process by apoptosis. Infected cultures treated for 24 h with the compounds showed similar effects, with drastic decrease in infection and the elimination of intracellular parasite at 1 mM without toxic effects on the host cells. Intracellular amastigotes showed progressive disorganization leading to the rupture and elimination of the parasite. The results strongly suggest that in presence of thiosemicarbazones and their derivate, intracellular amastigotes arrested the proliferation, leading to irreversible ultrastructural disorganization, death, and then elimination. When the intracellular T. cruzi elimination process was analysed, it showed that autophagy was present, in intriguing and new features to futures studies. In addition, our results in vitro also suggest that these compounds are promising molecules against intracellular T. cruzi when compared to the anti-proliferative drugs Hydroxyurea and Benznidazole.