Authors: Nunes, Felipe Oliveira
de Almeida, Júlio Menta
Ferreira, Alda Maria Teixeira
da Cruz, Letícia Alves
Jacob, Camila Mareti Bonin
Garcez, Walmir Silva
Garcez, Fernanda Rodrigues
Title: Antitrypanosomal butanolides from Aiouea trinervis
Language (ISO): en
Abstract: In a search for new antitrypanosomal agents in the Brazilian flora, the ethanol extract of the xylopodium from Aiouea trinervis (Lauraceae) exhibited in vitro activity against the epimastigote forms of Trypanosoma cruzi, the etiological agent of Chagas disease. Bioassay-guided chromatographic fractionation of the ethanol extract afforded three butanolides, isoobtusilactone A (1), epilitsenolide C2 (2), and epilitsenolide C1 (3). Butanolides 1 and 3 were more active against T. cruzi epimastigotes than the reference drug benznidazole (by 8.9-fold and 3.2-fold, respectively), while 2 proved inactive. Compounds 1 and 3 showed low cytotoxicity in mammalian Vero cells (CC50> 156 μmol L-1) and high selectivity index (SI) values for epimastigotes (SI = 56.8 and 28.6, respectively), and 1 was more selective than benznidazole (SI = 46.5). Butanolide 1 at 24 μmol L-1 also led to cell cycle alterations in epimastigote forms, and inhibited the growth of amastigote cells in more than 70 %. In silico ADMET properties of 1 were also analyzed and predicted favorable drug-like characteristics. This butanolide also complied with Lipinski’s rule of five and was not predicted as interference compound (PAINS). This is the first report on the isolation of these bioactive butanolides under the guidance of in vitro trypanocidal activity against T. cruzi.
Subject Headings: Aiouea trinervis
Trypanosoma cruzi
Anti-Trypanosoma activity
In silico ADMET properties
Issue Date: 2020-03-06
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Provenance: IfADo - Leibniz Research Centre for Working Environment and Human Factors, Dortmund
Citation: EXCLI Journal 2020;19:323-333
Appears in Collections:Original Articles 2020

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