Membrane composition modulates the interaction between a new class of antineoplastic agents deriving from aromatic 2-chloroethylureas and lipid bilayers: a solid-state NMR study.
We have investigated the interaction between a new class of antineoplastic agents derived from arylchloroethylureas (CEU) with three different model membranes by (31)P and (2)H solid-state NMR spectroscopy. First, we have prepared model membranes that mimic the mitochondrial inner (Mito IM) and outer (Mito OM) membranes and the endoplasmic reticulum membrane (End Ret). Our results indicate that the effects of the CEU derivatives on lipid bilayers are related to their cytotoxic activity. More specifically, a strong correlation is observed between the drug location in both the mitochondrial inner and outer membranes and its cytotoxicity. In addition, the results indicate that the lipid composition of the model membrane has a very important influence on the effects of CEUs. More specifically, a high proportion of cardiolipin in the mitochondrial inner membrane gives this system the highest fluidity and consequently, this model membrane is more rigidified by the presence of CEUs compared to the mitochondrial outer and endoplasmic reticulum membranes. Finally, the results propound a hypothesis for the location of CEUs in membranes.
Cronier
Francis
F
Département de Chimie, Centre de Recherche sur la Fonction, la Structure et l'Ingénierie des Protéines, Centre de Recherche en Sciences et Ingénierie des Macromolécules, Université Laval, Québec, Québec, Canada.
Patenaude
Alexandre
A
C-Gaudreault
René
R
Auger
Michèle
M
D000970:Antineoplastic Agents / Q000737:chemistry*; D008051:Lipid Bilayers; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D014508:Urea / Q000737:chemistry*
D000970:Antineoplastic Agents; D008051:Lipid Bilayers; D014508:Urea