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

[Display omitted] •Interaction of semi-synthetically prepared flavonolignan (7-O-galloylsilybin) with DNA is described.•We present evidence about interactions of flavonolignans with transition metals and DNA-damage.•Antioxidant and prooxidant effects of flavonolignans are investigated and discussed...

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Veröffentlicht in:Chemico-biological interactions 2013-10, Vol.205 (3), p.173-180
Hauptverfasser: Vacek, Jan, Zatloukalová, Martina, Desmier, Thomas, Nezhodová, Veronika, Hrbáč, Jan, Kubala, Martin, Křen, Vladimír, Ulrichová, Jitka, Trouillas, Patrick
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container_issue 3
container_start_page 173
container_title Chemico-biological interactions
container_volume 205
creator Vacek, Jan
Zatloukalová, Martina
Desmier, Thomas
Nezhodová, Veronika
Hrbáč, Jan
Kubala, Martin
Křen, Vladimír
Ulrichová, Jitka
Trouillas, Patrick
description [Display omitted] •Interaction of semi-synthetically prepared flavonolignan (7-O-galloylsilybin) with DNA is described.•We present evidence about interactions of flavonolignans with transition metals and DNA-damage.•Antioxidant and prooxidant effects of flavonolignans are investigated and discussed in general. 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 (Cu2+) 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.
doi_str_mv 10.1016/j.cbi.2013.07.006
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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 (Cu2+) 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. 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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 (Cu2+) 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. 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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 (Cu2+) 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.</abstract><cop>Ireland</cop><pub>Elsevier Ireland Ltd</pub><pmid>23872255</pmid><doi>10.1016/j.cbi.2013.07.006</doi><tpages>8</tpages></addata></record>
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ispartof Chemico-biological interactions, 2013-10, Vol.205 (3), p.173-180
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language eng
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subjects Albumin
Antioxidants
Antioxidants - chemistry
Antioxidants - metabolism
Antioxidants - pharmacology
Biphenyl Compounds
Biphenyl Compounds - metabolism
Copper
Copper - metabolism
DNA Damage
Electrochemical Techniques
Flavonolignans
Life Sciences
Luminescent Measurements
Molecular Dynamics Simulation
Nucleic acids
Pharmaceutical sciences
Picrates
Picrates - metabolism
Prooxidant effects
Silymarin
Silymarin - analogs & derivatives
Silymarin - chemistry
Silymarin - metabolism
Silymarin - pharmacology
Spectrophotometry, Ultraviolet
title Antioxidant, metal-binding and DNA-damaging properties of flavonolignans: A joint experimental and computational highlight based on 7-O-galloylsilybin
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