Scavengome of an Antioxidant

Hunyadi, Attila; Agbadua, Orinamhe Godwin; Takács, Gergely; Balogh, György Tibor

doi:10.26434/chemrxiv-2022-jl7rs-v2

Cited by 1 publication

(1 citation statement)

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“…These are well in line with the ‘scavengome’ concept that considers any small molecule antioxidants as pro-drug oxidizable by ROS/RNS to a broad chemical space of bioactive metabolites in a biological environment under oxidative stress [ 11 , 14 ]. To expand related knowledge on resveratrol, in the current study, it was our objective to use a chemical-oxidation-driven, diversity-oriented synthetic strategy to obtain its new bioactive derivatives.…”

Section: Introductionmentioning

confidence: 54%

Oxidized Resveratrol Metabolites as Potent Antioxidants and Xanthine Oxidase Inhibitors

et al. 2022

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Resveratrol is a well-known natural polyphenol with a plethora of pharmacological activities. As a potent antioxidant, resveratrol is highly oxidizable and readily reacts with reactive oxygen species (ROS). Such a reaction not only leads to a decrease in ROS levels in a biological environment but may also generate a wide range of metabolites with altered bioactivities. Inspired by this notion, in the current study, our aim was to take a diversity-oriented chemical approach to study the chemical space of oxidized resveratrol metabolites. Chemical oxidation of resveratrol and a bioactivity-guided isolation strategy using xanthine oxidase (XO) and radical scavenging activities led to the isolation of a diverse group of compounds, including a chlorine-substituted compound (2), two iodine-substituted compounds (3 and 4), two viniferins (5 and 6), an ethoxy-substituted compound (7), and two ethoxy-substitute,0d dimers (8 and 9). Compounds 4, 7, 8, and 9 are reported here for the first time. All compounds without ethoxy substitution exerted stronger XO inhibition than their parent compound, resveratrol. By enzyme kinetic and in silico docking studies, compounds 2 and 4 were identified as potent competitive inhibitors of the enzyme, while compound 2 and the viniferins acted as mixed-type inhibitors. Further, compounds 2 and 9 had better DPPH scavenging activity and oxygen radical absorbing capacity than resveratrol. Our results suggest that the antioxidant activity of resveratrol is modulated by the effect of a cascade of chemically stable oxidized metabolites, several of which have significantly altered target specificity as compared to their parent compound.

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Section: Introductionmentioning

confidence: 54%