Antitrypanosomal butanolides from Aiouea trinervis.

Content Provider	Europe PMC
Author	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
Copyright Year	2020
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.
Journal	EXCLI Journal
Volume Number	19
PubMed Central reference number	PMC7174576
PubMed reference number	32327956
e-ISSN	16112156
DOI	10.17179/excli2020-1088
Language	English
Publisher	Leibniz Research Centre for Working Environment and Human Factors
Publisher Date	2020-03-06
Access Restriction	Open
Rights License	This is an Open Access article distributed under the terms of the Creative Commons Attribution Licence (http://creativecommons.org/licenses/by/4.0/) You are free to copy, distribute and transmit the work, provided the original author and source are credited. Copyright © 2020 Nunes et al.
Subject Keyword	Aiouea trinervis Trypanosoma cruzi butanolides anti-Trypanosoma activity in silico ADMET properties
Content Type	Text
Resource Type	Article
Subject	Drug Discovery Pharmacology Animal Science and Zoology Molecular Medicine