Activity and Mode of Action of Flavonoids Compounds Against Intracellular and Extracellular Forms of Trypanosoma cruzi

This study investigates the in vitro activity of a number of flavonoids (kaempferol, quercetin, trifolin, and ace- tyl hyperoside) and their acetylated products: kaempferol acetate, quercetin acetate, trifolin acetate, and acetyl hyperoside acetate) isolated from the aerial parts of plant Consolida oliveriana against epimastigote, amastigote and metacyclic forms of T. cruzi, their cytotoxic against a host Vero-cell line and analyse the possible mechanism by which these molecules act. Acetylated compounds were potent T. cruzi epimastigote growth inhibitors with activity levels similar to those of benzni- dazole, used as the reference drug. These compounds, at the dosage IC25, decreased the ability of metacyclic forms to in- vade mammalian cells, their intracellular replications and transformation in trypomastigotes, with no toxicity to the host cells. The cells treated presented severe damage in their ultrastructure: intense vacuolization, and appearance of lysosomes as well as other residual bodies. The mitochondrial section appeared larger in size, with a swollen matrix. In addition, these compounds changed the excretion of end metabolites, primarily affecting acetate and succinate excretion, possibly by directly influencing certain enzymes or their synthesis. The potent tripanocidal activities of the flavons described here represent an exciting advance in the search for new antiprotozoal agents.