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

Ueno A.K.; Barcellos A.F.; Costa-Silva T.A.; Mesquita J.T.; Ferreira D.D.; Tempone A.G.; Romoff P.; Antar G.M.; Lago J.H.G.

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

Tipo

Artigo

Data de publicação

2018

Periódico

Fitoterapia

Citações (Scopus)

24

Autores

Ueno A.K.
Barcellos A.F.
Costa-Silva T.A.
Mesquita J.T.
Ferreira D.D.
Tempone A.G.
Romoff P.
Antar G.M.
Lago J.H.G.

Resumo

© 2017 Elsevier B.V.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 IC50 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 IC50 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.

Assuntos Scopus

Animals , Baccharis , Brazil , Cell Line , Diterpenes , Mice , Plant Components, Aerial , Plants, Medicinal , Trypanocidal Agents , Trypanosoma cruzi