Antitrypanosomal butanolides from Aiouea trinervis

Authors

  • Felipe Oliveira Nunes Instituto de Química, Universidade Federal de Mato Grosso do Sul, Av. Senador Filinto Muller 1555, 79074-460 Campo Grande-MS, Brazil
  • Júlio Menta de Almeida Instituto de Biociências, Universidade Federal de Mato Grosso do Sul, Av. Costa e Silva s/n, 79070-900 Campo Grande-MS, Brazil
  • Alda Maria Teixeira Ferreira Instituto de Biociências, Universidade Federal de Mato Grosso do Sul, Av. Costa e Silva s/n, 79070-900 Campo Grande-MS, Brazil
  • Letícia Alves da Cruz Instituto de Biociências, Universidade Federal de Mato Grosso do Sul, Av. Costa e Silva s/n, 79070-900 Campo Grande-MS, Brazil
  • Camila Mareti Bonin Jacob Instituto de Biociências, Universidade Federal de Mato Grosso do Sul, Av. Costa e Silva s/n, 79070-900 Campo Grande-MS, Brazil
  • Walmir Silva Garcez Instituto de Química, Universidade Federal de Mato Grosso do Sul, Av. Senador Filinto Muller 1555, 79074-460 Campo Grande-MS, Brazil
  • Fernanda Rodrigues Garcez Instituto de Química, Universidade Federal de Mato Grosso do Sul, Av. Senador Filinto Muller 1555, 79074-460 Campo Grande-MS, Brazil. Tel.: +55-67-33453579; E-mail: fernandargarcez@gmail.com

DOI:

https://doi.org/10.17179/excli2020-1088

Keywords:

Aiouea trinervis, Trypanosoma cruzi, butanolides, anti-Trypanosoma activity, in silico ADMET properties

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.

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Published

2020-03-06

How to Cite

Nunes, F. O., de Almeida, J. M., Ferreira, A. M. T., da Cruz, L. A., Jacob, C. M. B., Garcez, W. S., & Garcez, F. R. (2020). Antitrypanosomal butanolides from Aiouea trinervis. EXCLI Journal, 19, 323–333. https://doi.org/10.17179/excli2020-1088

Issue

Vol. 19 (2020)

Section

Original articles

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