title: Divalent Amino-Acid-Based Amphiphilic Antioxidants: Synthesis, Self-Assembling Properties, and Biological Evaluation.
abstract: 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.
authors: 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.
authors: Marie
authors: M
authors: Rosselin
authors: Avignon University , Laboratoire de Pharm-Ecologie Cardiovasculaire LAPEC EA4278, F-84000 Avignon, France.
authors: Grégory
authors: G
authors: Meyer
authors: 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.
authors: Pierre
authors: P
authors: Guillet
authors: 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.
authors: Thomas
authors: T
authors: Cheviet
authors: Avignon University , Laboratoire de Pharm-Ecologie Cardiovasculaire LAPEC EA4278, F-84000 Avignon, France.
authors: Guillaume
authors: G
authors: Walther
authors: Martin Luther University Halle-Wittenberg , Institute of Chemistry and Institute of Biochemistry/Biotechnology, von-Danckelmann-Platz 4, D-06120 Halle/Saale, Germany.
authors: Annette
authors: A
authors: Meister
authors: Department of Pharmaceutical Chemistry, School of Pharmacy, Faculty of Health Sciences, AUTh , Thessaloniki 54124, Greece.
authors: Dimitra
authors: D
authors: Hadjipavlou-Litina
authors: 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.
authors: Grégory
authors: G
authors: Durand
mesh_terms: D000596:Amino Acids / Q000737:chemistry*; D000818:Animals; D000975:Antioxidants / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000596:Amino Acids; D000975:Antioxidants