Antileishmanial and cytotoxic activities of ionic surfactants compared to those of miltefosine

• Published in: Colloids and surfaces, B, Biointerfaces Vol. 183; p. 110421
• Main Authors: Alonso, Lais, Cardoso, Éder Jeferson Souza, Gomes, Rodrigo Saar, Mendanha, Sebastião Antônio, Dorta, Miriam Leandro, Alonso, Antonio
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-11-2019
• Subjects: Antiprotozoal Agents - chemistry; Antiprotozoal Agents - pharmacology; Cell Line; Cell Membrane - drug effects; Cell Membrane - metabolism; Cell Membrane Permeability - drug effects; Cetrimonium - chemistry; Cetrimonium - pharmacology; Cytotoxins - chemistry; Cytotoxins - pharmacology; Electron paramagnetic resonance; Electron Spin Resonance Spectroscopy; Humans; Inhibitory Concentration 50; Leishmania; Leishmania braziliensis - drug effects; Leishmania braziliensis - growth & development; Leishmania braziliensis - metabolism; Macrophages; Macrophages - drug effects; Macrophages - parasitology; Membrane fluidity; Miltefosine; Molecular Dynamics Simulation; Phosphorylcholine - analogs & derivatives; Phosphorylcholine - pharmacology; Quaternary Ammonium Compounds - chemistry; Quaternary Ammonium Compounds - pharmacology; Sodium Dodecyl Sulfate - chemistry; Sodium Dodecyl Sulfate - pharmacology; Spin Labels; Stearic Acids - chemistry; Surface-Active Agents - chemistry; Surface-Active Agents - pharmacology; Surfactant; Miltefosine; Membrane fluidity; Electron paramagnetic resonance; Surfactant; Macrophages; Leishmania
• ISSN: 0927-7765; 1873-4367
• DOI: 10.1016/j.colsurfb.2019.110421

[Display omitted]
•The IC50 of miltefosine on Leishmania was cell-concentration dependent.•Ionic surfactants increased the dynamics of the parasite membrane proteins.•Miltefosine demonstrated similar in vitro results to a zwitterionic surfactant.
Using the electron paramagnetic resonance (EPR) of spin-labeled stearic acid and a spin label chemically attached to the membrane proteins, the interaction of miltefosine (MIL) and the ionic surfactants sodium dodecyl sulfate (SDS, anionic), cetyltrimethylammonium chloride (CTAC, cationic) and N-hexadecyl-N,N-dimethyl-3-ammonio-1-propanesulfonate (HPS, zwitterionic) with the plasma membrane of Leishmania (L.) amazonensis promastigotes was studied. The spin-label EPR data indicated that the four compounds studied have the ability to increase the molecular dynamics of membrane proteins to a large extent. Compared to the other compounds, SDS produced the smallest increases in dynamics and demonstrated the lowest antileishmanial activity and cytotoxicity to J774.A1 macrophages. The activities of the other three compounds were not different from each other, but CTAC had a stronger activity against L. amazonensis promastigotes at higher cellular concentrations (> 1 × 109 cells/mL) and was the most effective against L. amazonensis-infected macrophages. However, CTAC was also the most cytotoxic to macrophages. By measuring the IC50/CC50 values for assays of different cell concentrations, we estimated the membrane-water partition coefficient (KM/W) as well as the concentrations in the membrane (cm50) and aqueous phase (cw50) of the compounds at their IC50/CC50. Compared to the other compounds, SDS showed the lowest value of KM/W and the highest value of cm50. In all experiments in this study, the data for the zwitterionic molecules HPS and MIL were not significantly different.