Oxidized Resveratrol Metabolites as Potent Antioxidants and Xanthine Oxidase Inhibitors
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 ma...
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| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-09-01
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| Series: | Antioxidants |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-3921/11/9/1832 |
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| Summary: | 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 (<b>2</b>), two iodine-substituted compounds (<b>3</b> and <b>4</b>), two viniferins (<b>5</b> and <b>6</b>), an ethoxy-substituted compound (<b>7</b>), and two ethoxy-substitute,0d dimers (<b>8</b> and <b>9</b>). Compounds <b>4</b>, <b>7</b>, <b>8</b>, and <b>9</b> 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 <b>2</b> and <b>4</b> were identified as potent competitive inhibitors of the enzyme, while compound <b>3</b> and the viniferins acted as mixed-type inhibitors. Further, compounds <b>2</b> and <b>9</b> 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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| ISSN: | 2076-3921 |