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

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dc.contributor.authorBrito J.R.
dc.contributor.authorda Costa-Silva T.A.
dc.contributor.authorTempone A.G.
dc.contributor.authorFerreira E.A.
dc.contributor.authorLago J.H.G.
dc.date.accessioned2024-03-12T23:52:11Z
dc.date.available2024-03-12T23:52:11Z
dc.date.issued2019
dc.description.abstract© 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.
dc.description.volume137
dc.identifier.doi10.1016/j.fitote.2019.104251
dc.identifier.issn1873-6971
dc.identifier.urihttps://dspace.mackenzie.br/handle/10899/35215
dc.relation.ispartofFitoterapia
dc.rightsAcesso Restrito
dc.subject.otherlanguageAntitrypanosomal
dc.subject.otherlanguageNeolignans
dc.subject.otherlanguagePlasma membrane permeability
dc.subject.otherlanguageSaururaceae
dc.subject.otherlanguageSaururus cernuus
dc.subject.otherlanguageTrypanosoma cruzi
dc.titleDibenzylbutane neolignans from Saururus cernuus L. (Saururaceae) displayed anti-Trypanosoma cruzi activity via alterations in the mitochondrial membrane potential
dc.typeArtigo
local.scopus.citations9
local.scopus.eid2-s2.0-85068452451
local.scopus.subjectAnimals
local.scopus.subjectBrazil
local.scopus.subjectCells, Cultured
local.scopus.subjectGuaiacol
local.scopus.subjectLignans
local.scopus.subjectMacrophages, Peritoneal
local.scopus.subjectMembrane Potential, Mitochondrial
local.scopus.subjectMice, Inbred BALB C
local.scopus.subjectMolecular Structure
local.scopus.subjectPhytochemicals
local.scopus.subjectPlant Leaves
local.scopus.subjectReactive Oxygen Species
local.scopus.subjectSaururaceae
local.scopus.subjectTrypanocidal Agents
local.scopus.subjectTrypanosoma cruzi
local.scopus.updated2024-05-01
local.scopus.urlhttps://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85068452451&origin=inward
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