Antitrypanosomal butanolides from Aiouea trinervis .

Autor: Nunes FO; Instituto de Química, Universidade Federal de Mato Grosso do Sul, Av. Senador Filinto Muller 1555, 79074-460 Campo Grande-MS, Brazil., de Almeida JM; Instituto de Biociências, Universidade Federal de Mato Grosso do Sul, Av. Costa e Silva s/n, 79070-900 Campo Grande-MS, Brazil., Ferreira AMT; Instituto de Biociências, Universidade Federal de Mato Grosso do Sul, Av. Costa e Silva s/n, 79070-900 Campo Grande-MS, Brazil., da Cruz LA; Instituto de Biociências, Universidade Federal de Mato Grosso do Sul, Av. Costa e Silva s/n, 79070-900 Campo Grande-MS, Brazil., Jacob CMB; Instituto de Biociências, Universidade Federal de Mato Grosso do Sul, Av. Costa e Silva s/n, 79070-900 Campo Grande-MS, Brazil., Garcez WS; Instituto de Química, Universidade Federal de Mato Grosso do Sul, Av. Senador Filinto Muller 1555, 79074-460 Campo Grande-MS, Brazil., Garcez FR; Instituto de Química, Universidade Federal de Mato Grosso do Sul, Av. Senador Filinto Muller 1555, 79074-460 Campo Grande-MS, Brazil.
Jazyk: angličtina
Zdroj: EXCLI journal [EXCLI J] 2020 Mar 06; Vol. 19, pp. 323-333. Date of Electronic Publication: 2020 Mar 06 (Print Publication: 2020).
DOI: 10.17179/excli2020-1088
Abstrakt: 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 (CC 50 > 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 .
(Copyright © 2020 Nunes et al.)
Databáze: MEDLINE
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