Photoproducts of Indomethacin exhibit decreased hydroxyl radical scavenging and xanthine oxidase inhibition activities

Gi-Shih Lien, Chien Shu Chen, Wei-Yu Chen, Shih Hao Huang, Kur-Ta Cheng, Chun-Mao Lin, Su Hui Chao

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4 Citations (Scopus)

Abstract

Indomethacin (IN) is a widely used nonsteroidal anti-inflammatory drug. In this study, four photoproducts of IN (IN1-IN4) were produced and isolated from photoirradiated IN. This study investigated the abilities of IN and its photoproducts to scavenge hydroxyl radicals and inhibit xanthine oxidase (XO). The hydroxyl radical-scavenging activity was measured in vitro by electron spin resonance spectrometry using 5,5-dimethyl-1-pyrroline-N-oxide as a spin trapping agent. Enzyme activity was measured by continuous monitoring of uric acid formation, using xanthine as a substrate. The results showed that, among all the related products, IN has the strongest hydroxyl radical-scavenging (IC 50 = 65 μM) and XO inhibitory (IC50 = 86 μM) effects. To further understand the stereochemistry of the reactions between these IN derivatives and XO, we performed computer-aided molecular modeling. IN was the most potent inhibitor with the most favorable interaction in the reactive site. Various photoproducts exhibited affinity toward XO as a result of the absence of hydrogen bonding with molybdopterin domain.

Original languageEnglish
Pages (from-to)332-336
Number of pages5
JournalJournal of Food and Drug Analysis
Volume21
Issue number3
DOIs
Publication statusPublished - Sep 2013

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Keywords

  • Electron spin resonance
  • Hydroxyl radical
  • Indomethacin
  • Molecular modeling
  • Photoproduct
  • Xanthine oxidase

ASJC Scopus subject areas

  • Food Science
  • Pharmacology

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