Assessment of sesquiterpene lactones isolated from Mikania plants species for their potential efficacy against Trypanosoma cruzi and Leishmania sp

Four sesquiterpene lactones,mikanolide,deoxymikanolide,dihydromikanolide and scandenolide,were isolated by a bioassay-guided fractionation of mikania variifolia and mikania micrantha dichloromethane extracts. mikanolide and deoxymikanolide were the major compounds in both extracts (2.2% and 0.4% for mikania variifolia and 21.0% and 6.4% for mikania micrantha respectively,calculated on extract dry weight). mikanolide,deoxymikanolide and dihydromikanolide were active against trypanosoma cruzi epimastigotes (50% inhibitory concentrations of 0.7,0.08 and 2.5 μg/ml,for each compound respectively). these sesquiterpene lactones were also active against the bloodstream trypomastigotes (50% inhibitory concentrations for each compound were 2.1,1.5 and 0.3 μg/ml,respectively) and against amastigotes (50% inhibitory concentrations for each compound were 4.5,6.3 and 8.5 μg/ml,respectively). by contrast,scandenolide was not active on trypanosoma cruzi. besides,mikanolide and deoxymikanolide were also active on leishmania braziliensis promastigotes (50% inhibitory concentrations of 5.1 and 11.5 μg/ml,respectively). the four sesquiterpene lactones were tested for their cytotoxicity on thp 1 cells. deoxymikanolide presented the highest selectivity index for trypomastigotes (si = 54) and amastigotes (si = 12.5). in an in vivo model of trypanosoma cruzi infection,deoxymikanolide was able to decrease the parasitemia and the weight loss associated to the acute phase of the parasite infection. more importantly,while 100% of control mice died by day 22 after receiving a lethal t. cruzi infection,70% of deoxymikanolide-treated mice survived. we also observed that this compound increased tnf-α and il-12 production by macrophages,which could contribute to control t. cruzi infection. © 2017 laurella et al.