Photoproducts of indomethacin exhibit decreased hydroxyl radical scavenging and xanthine oxidase inhibition activities |
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| Authors: | 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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| Affiliation: | 1. Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan, ROC;2. School of Pharmacy, China Medical University, Taichung, Taiwan, ROC;3. Department of Pathology, College of Medicine, Taipei Medical University, Taipei, Taiwan, ROC;4. Department of Food and Beverage Management, Taipei College of Maritime Technology, Taipei, Taiwan, ROC;5. Department of Biochemistry, College of Medicine, Taipei Medical University, Taipei, Taiwan, ROC |
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| 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 (IC50 = 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. |
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| Keywords: | Electron spin resonance Hydroxyl radical Indomethacin Molecular modeling Photoproduct Xanthine oxidase |
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