Action of flavonoids against Trypanosoma cruzi epimastigotes

BARRERA PATRICIA; LOZANO ESTEBAN; CANO ROCIO; SOSA MIGUEL; CIFUENTE, DIEGO

Buenos Aires

Congreso; Drug Discovery for Neglected Diseases International Congress 2018; 2018

Trypanosoma cruzi is the causal etiologic agent of Chagas disease. It is estimated that around 8-10 million people are infected worldwide, being an endemic disease in Latin America (WHO 2015). In cultures, this parasite is mainly found in the epimastigote form and a low percentage in the infective form trypomastigote. At present, chemotherapy against T. cruzi is insufficient because the available drugs, Nifurtimox and Benznidazole, have limited activity, and show toxic side effects in patients. Therefore, the "screening" of purified molecules from plant sources, mainly plant leaves has become an important tool for the fight against Chagas disease. Many natural compounds, extracted from plants native to Argentina, have been shown to be effective against the parasite (Barrera et al., 2008; Lozano et al., 2012a, 2012b, 2015). Among them, flavonoids are an important family of molecules that have been widely studied. Objectives: In this work we analyze the effect of the flavonoids Xantomicrol (XML) and Salvigenin (SVG) isolated from Baccharis scandens and Apigenin (AGN) isolated from Larrea divaricata, on the growth of T. cruzi. Materials and methods: We used epimastigotes of T. cruzi (strain Dm28c) in axenic culture, grown in the absence or presence of different concentrations of the compounds. We evaluate both the stability of the compounds and the reversibility of their effects. In addition, we evaluated the effect of these flavonoids on the mitochondrial activity of the parasites through the MTT assay and the production of reactive oxygen species (ROS), by using the 2´, 7´-Diclocrofluorescein diacetate (H2DCFDA) probe. Results and discussion: All the compounds showed an antiproliferative effect on epimastigotes, even at low concentrations. In addition, this effect was irreversible even in the short term (1 h) of exposure to the compounds. We observed that SVG significantly decreases the mitochondrial activity of the parasites, at all the concentrations tested (1, 2, 5 and 10 μg / ml). In contrast, AGN only decreased mitochondrial activity at concentrations of 10 μg / ml and XML affected the mitochondrial activity of epimastigotes at concentrations of 5 and 10 μg / ml. These alterations are related to ROS production observed with each treatment. Conclusions: From these results it is necessary to identify the molecular targets of the parasites for the action of these drugs and to determine how they affect the life cycle of T cruzi.