Antitrypanosomal activity and evaluation of the mechanism of action of diterpenes from aerial parts of Baccharis retusa (Asteraceae).

Baccharis retusa, a medicinal Brazilian plant from Asteraceae, has been used in Brazilian folk medicine to treatment of several illnesses, including parasitic diseases. Bioactivity-guided fractionation of the n-hexane extract from the aerial parts of B. retusa resulted in the isolation and characterization of three active related diterpenes: ent -15β-senecioyl-oxy-kaur-16-en-19-oic acid ( 1 ), ent -kaur-16-en-19-oic ( 2 ) and ent -16-oxo-17-nor-kauran-19-oic ( 3 ) acids. The structures of isolated compounds were defined by spectroscopic analysis, including NMR and HRESIMS. Antitrypanosomal activity of 1–3 was performed against cell-derived trypomastigotes using the colorimetric resazurin assay. The obtained results demonstrated that isolated compounds displayed a reduced toxicity against NCTC cells and were effective against the trypomastigote forms of T. cruzi with IC 50 values of 3.8 μM ( 1 ), 75.3 μM ( 2 ) and 44.2 μM ( 3 ). Additionally, compound 3 displayed activity against amastigote forms of T. cruzi with IC 50 of 83.2 μM. Compound 1 displayed the highest selectivity index (SI) when considered the trypomastigote forms, and its effect in the plasma membrane of parasite was evaluated using the fluorescent probe SYTOX Green. A considerable permeabilization (57%) in the membrane of the parasite was observed when compared to the untreated trypomastigotes. These data demonstrate, for the first time, the antitrypanosomal activity and mechanism of action of 1 and related compounds 2 and 3 , obtained from aerial parts of B. retusa . [ABSTRACT FROM AUTHOR]