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

Autor(es)

Ueno, Anderson K. ^[1] ; Barcellos, Aline F. ^[2] ; Costa-Silva, Thais A. ^[2] ; Mesquita, Juliana T. ^[3] ; Ferreira, Daiane D. ^[3] ; Tempone, Andre G. ^[3] ; Romoff, Paulete ^[4] ; Antar, Guilherme M. ^[5] ; Lago, Joao Henrique G. ^[2]

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo, Inst Environm Chem & Pharmaceut Sci, BR-09972270 Sao Paulo - Brazil

^[2] Fed Univ ABC, Ctr Nat Sci & Humanities, BR-09210580 Sao Paulo - Brazil

^[3] Adolfo Lutz Inst, Ctr Parasitol & Mycol, BR-01246000 Sao Paulo - Brazil

^[4] Univ Prebiteriana Mackenzie, Sch Engn, BR-01302907 Sao Paulo - Brazil

^[5] Univ Sao Paulo, Inst Biosci, Dept Bot, BR-05508090 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Fitoterapia; v. 125, p. 55-58, MAR 2018.
• Citações Web of Science: 7

Resumo

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)

• Processo FAPESP: 15/23403-9 - Estudo Pré-Clínico Racional de Novos Candidatos a Fármacos em Protozooses Negligenciadas Utilizando Abordagens Farmacocinéticas
• Beneficiário: André Gustavo Tempone Cardoso
• Modalidade de apoio: Auxílio à Pesquisa - Regular
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• Modalidade de apoio: Auxílio à Pesquisa - Regular
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• Beneficiário: Geanne Alexsandra Alves Conserva
• Modalidade de apoio: Bolsas no Brasil - Mestrado