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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Brito, Juliana R. [1] ; Da Costa-Silva, Thais A. [2] ; Tempone, Andre G. [3] ; Ferreira, Edgard A. [4] ; Lago, Joao Henrique G. [2]
Total Authors: 5
[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
Total Affiliations: 4
Document type: Journal article
Source: Fitoterapia; v. 137, SEP 2019.
Web of Science Citations: 0

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)

FAPESP's process: 18/10279-6 - Selection and Optimization of New Drug Candidates for Leishmaniasis and Chagas Disease
Grantee:André Gustavo Tempone Cardoso
Support Opportunities: Regular Research Grants
FAPESP's process: 18/07885-1 - Biomolecules from plant species of remnant areas of the Atlantic Forest and Cerrado to treat neglected tropical diseases - chemical and pharmacological aspects
Grantee:João Henrique Ghilardi Lago
Support Opportunities: BIOTA-FAPESP Program - Regular Research Grants