Synergistic effects of parthenolide and benznidazole on Trypanosoma cruzi

Parthenolide previously isolated from Tanacetum vulgare was tested for its in vitro combinatory effect with benznidazole against Trypanosoma cruzi. Parthenolide showed a strong synergistic activity against epimastigote forms, reducing 23-fold the concentration of benznidazole necessary to inhibit 50% of cell growth (IC50 of 1.6 to 0.07 μg/ml) when in combination with parthenolide. In addition, an additive effect against trypomastigote forms (FIC 1.06), followed by an antagonistic effect on the cytotoxicity (FIC 2.36), was observed for the combination of both drugs. Parthenolide induced morphological alterations in the body shape of trypomastigote forms, causing rounding and shortening of the parasite and loss of integrity of the plasma membrane, as previously described by other workers.