Permeability of 5-aminolevulinic acid oxime derivatives in lipid membranes
| Autor: | Emma S. E. Eriksson, Leif A. Eriksson, Edvin Erdtman |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
5-ALA derivatives
Membrane permeability Stereochemistry Cellbiologi oximes 010402 general chemistry 01 natural sciences chemistry.chemical_compound prodrugs 0103 physical sciences Teoretisk kemi Physical and Theoretical Chemistry 5-ALA Lipid bilayer Theoretical Chemistry membrane Cancer och onkologi 010304 chemical physics Protoporphyrin IX Bilayer Cell Biology Permeation Oxime molecular dynamics 0104 chemical sciences Membrane chemistry photodynamic therapy Permeability (electromagnetism) Cancer and Oncology Biophysics permeability |
| Popis: | The endogenous molecule 5-aminolevulinic acid (5ALA) and its methyl ester (Me-5ALA) have been used as prodrugs in photodynamic treatment of actinic keratosis and superficial non-melanoma skin cancers for over a decade. Recently, a novel set of 5ALA derivatives based on introducing a hydrolyzable oxime functionality was proposed and shown to generate considerably stronger onset of the photoactive molecule protoporphyrin IX (PpIX) in the cells. In the current work, we employ molecular dynamics simulation techniques to explore whether the higher intercellular concentration of PpIX caused by the oxime derivatives is related to enhanced membrane permeability, or whether other factors contribute to this. It is concluded that the oximes show overall similar accumulation at the membrane headgroup regions as the conventional derivatives and that the transmembrane permeabilities are in general close to that of 5ALA. The highest permeability of all compounds explored is found for Me-5ALA, which correlates with a considerably lower fee energy barrier at the hydrophobic bilayer center. The high PpIX concentration must hence be sought in other factors, where slow hydrolysis of the oxime functionality is a plausible reason, enabling stronger buildup of PpIX over time. |
| Databáze: | OpenAIRE |
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