Antioxidant, metal-binding and DNA-damaging properties of flavonolignans: A joint experimental and computational highlight based on 7-O-galloylsilybin

Autor: Veronika Nezhodová, Vladimír Křen, Patrick Trouillas, Jan Hrbac, Jitka Ulrichová, Thomas Desmier, Martina Zatloukalová, Jan Vacek, Martin Kubala
Přispěvatelé: Centre of Biocatalysis and Biotransformation, Institute of Microbiology, Czech Academy of Sciences [Prague] (CAS), Pharmacologie des Immunosuppresseurs et de la Transplantation (PIST), Université de Limoges (UNILIM)-CHU Limoges-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Institut National de la Santé et de la Recherche Médicale (INSERM), Marquet, Pierre
Rok vydání: 2013
Předmět:
Antioxidant
DNA damage
DPPH
Stereochemistry
medicine.medical_treatment
Molecular Dynamics Simulation
010402 general chemistry
Toxicology
01 natural sciences
Antioxidants
Metal
Flavonolignans
chemistry.chemical_compound
Picrates
MESH: Spectrophotometry
Ultraviolet
medicine
Flavonolignan
Moiety
MESH: Molecular Dynamics Simulation
MESH: DNA Damage
MESH: Picrates
010405 organic chemistry
Biphenyl Compounds
MESH: Antioxidants
Electrochemical Techniques
General Medicine
[SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences
MESH: Electrochemical Techniques
0104 chemical sciences
[SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences
MESH: Copper
MESH: Luminescent Measurements
chemistry
Polyphenol
visual_art
Luminescent Measurements
visual_art.visual_art_medium
Spectrophotometry
Ultraviolet
Copper
MESH: Biphenyl Compounds
DNA Damage
Silymarin
MESH: Silymarin
Zdroj: Chem Biol Interact
Chem Biol Interact, 2013, 205 (3), pp.173-80. ⟨10.1016/j.cbi.2013.07.006⟩
ISSN: 0009-2797
DOI: 10.1016/j.cbi.2013.07.006
Popis: International audience; Besides the well-known chemoprotective effects of polyphenols, their prooxidant activities via interactions with biomacromolecules as DNA and proteins are of the utmost importance. Current research focuses not only on natural polyphenols but also on synthetically prepared analogs with promising biological activities. In the present study, the antioxidant and prooxidant properties of a semi-synthetic flavonolignan 7-O-galloylsilybin (7-GSB) are described. The presence of the galloyl moiety significantly enhances the antioxidant capacity of 7-GSB compared to that of silybin (SB). These findings were supported by electrochemistry, DPPH (2,2-diphenyl-1-picrylhydrazyl) scavenging activity, total antioxidant capacity (CL-TAC) and DFT (density functional theory) calculations. A three-step oxidation mechanism of 7-GSB is proposed at pH 7.4, in which the galloyl moiety is first oxidized at Ep,1=+0.20V (vs. Ag/AgCl3M KCl) followed by oxidation of the 20-OH (Ep,2=+0.55V) and most probably 5-OH (Ep,3=+0.95V) group of SB moiety. The molecular orbital analysis and the calculation of O-H bond dissociation enthalpies (BDE) fully rationalize the electrooxidation processes. The metal (Cu(2+)) complexation of 7-GSB was studied, which appeared to involve both the galloyl moiety and the 5-OH group. The prooxidant effects of the metal-complexes were then studied according to their capacity to oxidatively induce DNA modification and cleavage. These results paved the way towards the conclusion that 7-O-galloyl substitution to SB concomitantly (i) enhances antioxidant (ROS scavenging) capacity and (ii) decreases prooxidant effect/DNA damage after Cu complexation. This multidisciplinary approach provides a comprehensive mechanistic picture of the antioxidant vs. metal-induced prooxidant effects of flavonolignans at the molecular level, under ex vivo conditions.
Databáze: OpenAIRE
Externí odkaz: