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Dibenzylbutane neolignans from Saururus cernuus L. (Saururaceae) displayed anti-Trypanosoma cruzi activity via alterations in the mitochondrial membrane potential.
Brito, Juliana R; da Costa-Silva, Thais A; Tempone, Andre G; Ferreira, Edgard A; Lago, João Henrique G.
Afiliação
  • Brito JR; Institute of Environmental, Chemical and Pharmaceutical Sciences, Federal University of São Paulo, Diadema, SP 09972-270, Brazil.
  • da Costa-Silva TA; Center of Natural Sciences and Humanities, Federal University of ABC, Santo Andre, SP 09210-180, Brazil.
  • Tempone AG; Centre for Parasitology and Mycology, Instituto Adolfo Lutz, São Paulo, SP 01246-902, Brazil.
  • Ferreira EA; School of Engineering, Mackenzie Presbyterian University, São Paulo, SP 01302-907, Brazil. Electronic address: edgard.ferreira@mackenzie.br.
  • Lago JHG; Center of Natural Sciences and Humanities, Federal University of ABC, Santo Andre, SP 09210-180, Brazil. Electronic address: joao.lago@ufabc.edu.br.
Fitoterapia ; 137: 104251, 2019 Sep.
Article em En | MEDLINE | ID: mdl-31271783
The 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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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Tripanossomicidas / Trypanosoma cruzi / Lignanas / Saururaceae / Potencial da Membrana Mitocondrial Limite: Animals País/Região como assunto: America do sul / Brasil Idioma: En Revista: Fitoterapia Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Brasil País de publicação: Holanda
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Tripanossomicidas / Trypanosoma cruzi / Lignanas / Saururaceae / Potencial da Membrana Mitocondrial Limite: Animals País/Região como assunto: America do sul / Brasil Idioma: En Revista: Fitoterapia Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Brasil País de publicação: Holanda