In vitro antileishmanial and cytotoxic activities of nerolidol are associated with changes in plasma membrane dynamics
| Autor: | Antonio Alonso, Pablo José Gonçalves, Miriam Leandro Dorta, Sebastião Antonio Mendanha, Kelly Souza Fernandes, Lais Alonso, Rodrigo Saar Gomes |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Membrane Fluidity 030106 microbiology Biophysics Antiprotozoal Agents Antineoplastic Agents Biochemistry Hemolysis Cell membrane 03 medical and health sciences chemistry.chemical_compound Mice Membrane fluidity medicine Animals Amastigote Cytotoxicity Nerolidol Leishmania Mice Inbred BALB C biology Cell Membrane Electron Spin Resonance Spectroscopy Cell Biology biology.organism_classification Antiparasitic agent 030104 developmental biology medicine.anatomical_structure chemistry Cell culture assays Sesquiterpenes |
| Zdroj: | Biochimica et biophysica acta. Biomembranes. 1861(6) |
| ISSN: | 1879-2642 |
| Popis: | 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) spectroscopy 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 interactions 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 promastigotes 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. |
| Databáze: | OpenAIRE |
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