Dibenzylbutane neolignans from Saururus cernuus L. (Saururaceae) displayed anti-Trypanosoma cruzi activity via alterations in the mitochondrial membrane potential
Tipo
Artigo
Data de publicação
2019
Periódico
Fitoterapia
Citações (Scopus)
9
Autores
Brito J.R.
da Costa-Silva T.A.
Tempone A.G.
Ferreira E.A.
Lago J.H.G.
da Costa-Silva T.A.
Tempone A.G.
Ferreira E.A.
Lago J.H.G.
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Resumo
© 2019The MeOH extract from leaves of Saururus cernuus L. (Saururaceae) displayed in vitro activity against trypomastigote forms of T. cruzi (100% of parasite death at 200 μg/mL), suggesting the presence of bioactive compounds. Thus, the bioactivity-guided fractionation was carried out, leading to the isolation of three related neolignan derivatives, identified as threo-austrobailignan-5 (1), threo-austrobailignan-6 (2), and threo-dihydroguaiaretic acid (3). Anti-T. cruzi activity of compounds 1–3 was performed against cell-derived trypomastigotes and intracellular amastigotes. Additionally, the mammalian cytotoxicity was investigated using NCTC cells. Compound 2 was the most effective against extracellular trypomastigotes with IC50 of 3.7 μM, while compound 3 showed activity in both clinically relevant forms of the parasite, trypomastigotes and amastigotes, with IC50 values of 7.0 and 16.2 μM, respectively. However, the structurally related compound 1 was inactive. Based on these results, compounds 2 and 3 were selected to evaluate the mechanism of cellular death. Compound 2 induced alteration in the plasma membrane permeability and consequently in the ROS levels after 120 min of incubation. By using flow cytometry and fluorescence microscopy, compound 3 showed alterations in the mitochondrial membrane potential (ΔΨm) of trypomastigotes. Considering the promising chemical and biological properties of neolignans 2 and 3, these compounds could be used as starting points to develop new lead compounds for Chagas disease.
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Animals , Brazil , Cells, Cultured , Guaiacol , Lignans , Macrophages, Peritoneal , Membrane Potential, Mitochondrial , Mice, Inbred BALB C , Molecular Structure , Phytochemicals , Plant Leaves , Reactive Oxygen Species , Saururaceae , Trypanocidal Agents , Trypanosoma cruzi