Abstract
The damage of cell membranes induced by photosensitive drugs has attracted the significant attention of researchers in various fields of medicine. Ketoprofen (KP) is known to be the most photosensitive among the nonsteroidal anti-inflammatory drugs. The phototoxic side effects of KP and other non-steroidal anti-inflammatory drugs are associated with the action of free radicals, but there is insufficient information about the nature of these radicals. In the present study, free radicals formed upon KP irradiation within lipid membranes were studied using nuclear magnetic resonance (NMR) and chemically induced dynamic nuclear polarization (CIDNP) methods, as well as a molecular dynamics simulation. Our study confirmed the effective penetration of KP into the lipid bilayer and showed a significant effect of the nature of the medium on the photolysis mechanism. While, in a homogeneous solution, the main channel of KP photolysis is free radical-mediated monomolecular decomposition with formation of radical pairs of benzyl and CO2H● radicals, then, in the lipid membrane, the reaction route shifts towards the bimolecular reaction of KP photoreduction. In addition, the effect of the presence an electron donor (the amino acid tryptophan) on lipid oxidation has been studied. It was found that photoreaction of KP with tryptophan proceeds more efficiently than with lipid molecules.
Highlights
The interaction of photosensitive drugs with cell membranes has attracted significant attention of researchers in various fields of medicine
Free radicals formed upon KP irradiation within lipid membranes were studied using nuclear magnetic resonance (NMR) and chemically induced dynamic nuclear polarization (CIDNP) methods, as well as a molecular dynamics simulation
We applied the NMR technique and molecular dynamic simulation to study the interaction of KP molecules, in protonated and deprotonated forms, with lipid bilayer and amino acid tryptophan
Summary
The interaction of photosensitive drugs with cell membranes has attracted significant attention of researchers in various fields of medicine. Membranes provide stable cell functioning and transport of small molecules and ions between the cell and its environment. The damage of cell membranes caused by photoinduced oxidation of lipid molecules and membraneassociated peptides may induce various phototoxic and photoallergic reactions. These reactions are described in a number of reviews and research articles [1,2,3]. FTKhPe intaerpahcotisopnholfipKiPd with the lipid bilayer and tryptophan molecules was investigated by 1H NMR techniques. The interact3ioofn of KP with the lipid bilayer and tryptophan molecules was investigated by 1H NMR techniques and molecular dynamic (MD) simulations at different pH.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
