Photoproducts of Indomethacin exhibit decreased hydroxyl radical scavenging and xanthine oxidase inhibition activities
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. Copyright © 2013, Food and Drug Administration, Taiwan. Published by Elsevier Taiwan LLC. All rights reserved.
Lien, G.-S.; Chen, C.-S.; Chen, W.-Y.; Huang, S.-H.; Cheng, K.-T.; Lin, C.-M.; and Chao, S.-H.
"Photoproducts of Indomethacin exhibit decreased hydroxyl radical scavenging and xanthine oxidase inhibition activities,"
Journal of Food and Drug Analysis: Vol. 21
, Article 2.
Available at: https://doi.org/10.1016/j.jfda.2013.07.013