Author:
Dagnino Ana Paula Aquistapase,Mesquita Camila Saporiti,Dorneles Gilson Pires,Teixeira Vivian de Oliveira Nunes,de Barros Francisco Maikon Corrêa,Vidal Ccana-Ccapatinta Gari,Fonseca Simone Gonçalves,Monteiro Marta Chagas,Júnior Luiz Carlos Rodrigues,Peres Alessandra,von Poser Gilsane Lino,Romão Pedro Roosevelt Torres
Abstract
AbstractBioactive molecules isolated from plants are promising sources for the development of new therapies against leishmaniasis. We investigated the leishmanicidal activity of cariphenone A (1), isouliginosin B (2) and uliginosin B (3) isolated from Hypericum species. Promastigotes and amastigotes of Leishmania amazonensis were incubated with compounds 1–3 at concentrations 1–100 µm for 48 h. The anti-promastigote effect of compounds was also tested in combinations. The cytotoxicity against macrophages and human erythrocytes were determined using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) method and hemolysis assay, respectively. The compounds 1–3 showed high leishmanicidal activity against promastigotes, IC50 values of 10.5, 17.5 and 11.3 µm, respectively. Synergistic interactions were found to the associations of compounds 1 and 2 [Σ fractional inhibitory concentration (FIC) = 0.41], and 2 and 3 (ΣFIC = 0.28) on promastigotes. All Hypericum compounds induced mitochondrial hyperpolarization and reactive oxygen species production in promastigotes. The compounds showed low cytotoxicity toward mammalian cells, high selectivity index and killed intracellular amastigotes probably mediated by oxidative stress. These results indicate that these compounds are promising candidates for the development of drugs against leishmaniasis.
Publisher
Cambridge University Press (CUP)
Subject
Infectious Diseases,Animal Science and Zoology,Parasitology
Cited by
12 articles.
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