Ueno, Anderson K.
Barcellos, Aline F.
Costa-Silva, Thais A.
Mesquita, Juliana T.
Ferreira, Daiane D.
Tempone, Andre G.
Antar, Guilherme M.
Lago, Joao Henrique G.
Total Authors: 9
 Univ Fed Sao Paulo, Inst Environm Chem & Pharmaceut Sci, BR-09972270 Sao Paulo - Brazil
 Fed Univ ABC, Ctr Nat Sci & Humanities, BR-09210580 Sao Paulo - Brazil
 Adolfo Lutz Inst, Ctr Parasitol & Mycol, BR-01246000 Sao Paulo - Brazil
 Univ Prebiteriana Mackenzie, Sch Engn, BR-01302907 Sao Paulo - Brazil
 Univ Sao Paulo, Inst Biosci, Dept Bot, BR-05508090 Sao Paulo - Brazil
Total Affiliations: 5
Web of Science Citations:
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-15 beta-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 mu M (1), 75.3 mu M (2) and 44.2 mu M (3). Additionally, compound 3 displayed activity against amastigote forms of T. cruzi with IC50 of 83.2 mu M. 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. (AU)