Terpenes increase the lipid dynamics in the Leishmania plasma membrane at concentrations similar to their IC50 values
Carregando...
Data
2014-08
Título da Revista
ISSN da Revista
Título de Volume
Editor
Resumo
Although many terpenes have shown antitumor, antibacterial, antifungal, and antiparasitic activity, the mechanism of action
is not well established. Electron paramagnetic resonance (EPR) spectroscopy of the spin-labeled 5-doxyl stearic acid
revealed remarkable fluidity increases in the plasma membrane of terpene-treated Leishmania amazonensis promastigotes.
For an antiproliferative activity assay using 56106 parasites/mL, the sesquiterpene nerolidol and the monoterpenes (+)-
limonene, a-terpineol and 1,8-cineole inhibited the growth of the parasites with IC50 values of 0.008, 0.549, 0.678 and
4.697 mM, respectively. The IC50 values of these terpenes increased as the parasite concentration used in the cytotoxicity
assay increased, and this behavior was examined using a theoretical treatment of the experimental data. Cytotoxicity tests
with the same parasite concentration as in the EPR experiments revealed a correlation between the IC50 values of the
terpenes and the concentrations at which they altered the membrane fluidity. In addition, the terpenes induced small
amounts of cell lysis (4–9%) at their respective IC50 values. For assays with high cell concentrations (26109 parasites/mL), the
incorporation of terpene into the cell membrane was very fast, and the IC50 values observed for 24 h and 5 min-incubation
periods were not significantly different. Taken together, these results suggest that terpene cytotoxicity is associated with
the attack on the plasma membrane of the parasite. The in vitro cytotoxicity of nerolidol was similar to that of miltefosine,
and nerolidol has high hydrophobicity; thus, nerolidol might be used in drug delivery systems, such as lipid nanoparticles to
treat leishmaniasis.
Descrição
Palavras-chave
Citação
CAMARGOS, Heverton Silva; MOREIRA, Rodrigo Alves; MENDANHA, Sebastião Antonio; FERNANDES, Kelly Souza; DORTA, Miriam Leandro; ALONSO, Antonio. Terpenes increase the lipid dynamics in the Leishmania plasma membrane at concentrations similar to their IC50 values. Plos One, San Francisco, v. 9, n. 8, e104429, Aug. 2014.