Rosselin Marie, Meyer Grégory, Guillet Pierre, Cheviet Thomas, Walther Guillaume, Meister Annette, Hadjipavlou-Litina Dimitra, Durand Grégory
Institut des Biomolécules Max Mousseron (UMR 5247 CNRS-Université Montpellier-ENSCM) & Avignon University, Equipe Chimie Bioorganique et Systèmes Amphiphiles, 301 rue Baruch de Spinoza, F-84916 Cedex 9 Avignon, France.
Avignon University , Laboratoire de Pharm-Ecologie Cardiovasculaire LAPEC EA4278, F-84000 Avignon, France.
Bioconjug Chem. 2016 Mar 16;27(3):772-81. doi: 10.1021/acs.bioconjchem.6b00002. Epub 2016 Feb 22.
We report herein the synthesis of a divalent amphiphilic carrier onto which α-phenyl-N-tert-butyl nitrone (PBN) and 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (Trolox) antioxidants were grafted to give the divalent derivative called FATxPBN. The divalent carrier consists of two lysine amino acids as a scaffold upon which the antioxidant moieties are grafted, a perfluorinated chain that supplies hydrophobicity, and a sugar-based polar headgroup that ensures water solubility. For the sake of comparison, a divalent PBN derivative called FADiPBN was also synthesized. The self-aggregation properties of FATxPBN and FADiPBN were studied by means of surface tension, dynamic light scattering, and transmission electron microscopy methods, and showed they form small micelles (i.e., 12 and 6 nm diameter, respectively) at submillimolar concentrations (i.e., 0.01 and 0.05 mM, respectively), in agreement with partition coefficient values. The superior antioxidant properties of FATxPBN over FADiPBN and the parent compounds PBN and Trolox were demonstrated using in vitro ABTS(•+) reduction (98%) and soybean lipoxygenase inhibition (94%) assays. Finally, FATxPBN was found to significantly inhibit hyperglycemia-induced toxicity on an ex-vivo rat model, demonstrating its potency as a bioactive antioxidant against oxidative stress-induced damage.
