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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Dibenzylbutane neolignans from Saururus cernuus L. (Saururaceae) displayed anti-Trypanosoma cruzi activity via alterations in the mitochondrial membrane potential

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Autor(es):
Brito, Juliana R. [1] ; Da Costa-Silva, Thais A. [2] ; Tempone, Andre G. [3] ; Ferreira, Edgard A. [4] ; Lago, Joao Henrique G. [2]
Número total de Autores: 5
Afiliação do(s) autor(es):
[1] Univ Fed Sao Paulo, Inst Environm Chem & Pharmaceut Sci, BR-09972270 Diadema, SP - Brazil
[2] Fed Univ ABC, Ctr Nat Sci & Humanities, BR-09210180 Santo Andre, SP - Brazil
[3] Adolfo Lutz Inst, Ctr Parasitol & Mycol, BR-01246902 Sao Paulo, SP - Brazil
[4] Univ Prebiteriana Mackenzie, Sch Engn, BR-01302907 Sao Paulo, SP - Brazil
Número total de Afiliações: 4
Tipo de documento: Artigo Científico
Fonte: Fitoterapia; v. 137, SEP 2019.
Citações Web of Science: 0
Resumo

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 mu g/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 mu M, 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 mu M, 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 (Delta psi(m)) 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. (AU)

Processo FAPESP: 18/10279-6 - Seleção e otimização de novos candidatos a fármacos para Leishmaniose e Doença de Chagas
Beneficiário:André Gustavo Tempone Cardoso
Linha de fomento: Auxílio à Pesquisa - Regular
Processo FAPESP: 18/07885-1 - Biomoléculas oriundas de espécies vegetais de áreas remanescentes da Mata Atlântica e do Cerrado para tratamento de doenças tropicais negligenciadas - aspectos químicos e farmacológicos
Beneficiário:João Henrique Ghilardi Lago
Linha de fomento: Auxílio à Pesquisa - Programa BIOTA - Regular