In vitro antileishmanial and cytotoxic activities of nerolidol are associated with changes in plasma membrane dynamics
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2019
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The sesquiterpene nerolidol is a membrane-active compound that has demonstrated antitumor, antibacterial,
antifungal and antiparasitic activities. In this study, we used electron paramagnetic resonance (EPR) spectro scopy and biophysical parameters determined via cell culture assays to study the mechanisms underlying the in
vitro antileishmanial activity of nerolidol. The EPR spectra of a spin-labeled stearic acid indicated notable in teractions of nerolidol with the cell membrane of Leishmania amazonensis amastigotes. The nerolidol IC50 values
in L. amazonensis amastigotes and promastigotes were found to depend on the cell concentration used in the
assay. This dependence was described by an equation that considers various cell suspension parameters, such as
the 50% inhibitory concentrations of nerolidol in the cell membrane (cm50) and the aqueous phase (cw50) and the
membrane-water partition coefficient of nerolidol (KM/W). Via cytotoxicity (CC50) and hemolytic potential
(HC50) data, these parameters were also determined for nerolidol in macrophages and erythrocytes. With a cw50
of 125 μM, macrophages were less sensitive to nerolidol than amastigotes and promastigotes, which had mean
cw50 values of 56 and 74 μM, respectively. The estimated cm50 values of nerolidol for amastigotes and pro mastigotes and macrophages were between 2.6 and 3.0 M, indicating substantial accumulation of nerolidol in
the cell membrane. In addition, the spin-label EPR data indicated that membrane dynamic changes occurred in L.
amazonensis amastigotes at concentrations similar to the nerolidol IC50 value.
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Nerolidol, Leishmania, Macrophages, Membrane fluidity
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ALONSO, Lais; FERNANDES, Kelly Souza; MEDANHA, Sebastião Antônio; GONÇALVES, Pablo José; GOMES, Rodrigo Saar; DORTA, Miriam Leandro; ALONSO, Antonio. In vitro antileishmanial and cytotoxic activities of nerolidol are associated with changes in plasma membrane dynamics. Biochimica et Biophysica Acta (BBA) - Biomembranes, Amsterdam, v. 1861, n. 6, p. 1049-1056, 2019. DOI: 10.1016/j.bbamem.2019.03.006. Disponível em: https://pubmed.ncbi.nlm.nih.gov/30890467/. Acesso em: 26 maio 2023.