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

Research output: Contribution to journalArticle

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

Fingerprint

xanthine oxidase
indomethacin
Xanthine Oxidase
hydroxyl radicals
Indomethacin
Hydroxyl Radical
inhibitory concentration 50
Molecular Computers
Spin Trapping
xanthine
Xanthine
hydrogen bonding
nonsteroidal anti-inflammatory agents
electron paramagnetic resonance spectroscopy
stereochemistry
Electron Spin Resonance Spectroscopy
uric acid
Hydrogen Bonding
Uric Acid
active sites

Keywords

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

ASJC Scopus subject areas

  • Food Science
  • Pharmacology

Cite this

Photoproducts of Indomethacin exhibit decreased hydroxyl radical scavenging and xanthine oxidase inhibition activities. / Lien, Gi-Shih; Chen, Chien Shu; Chen, Wei-Yu; Huang, Shih Hao; Cheng, Kur-Ta; Lin, Chun-Mao; Chao, Su Hui.

In: Journal of Food and Drug Analysis, Vol. 21, No. 3, 09.2013, p. 332-336.

Research output: Contribution to journalArticle

@article{0336e31a22374a9fb73bd618edd8d9ed,
title = "Photoproducts of Indomethacin exhibit decreased hydroxyl radical scavenging and xanthine oxidase inhibition activities",
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.",
keywords = "Electron spin resonance, Hydroxyl radical, Indomethacin, Molecular modeling, Photoproduct, Xanthine oxidase",
author = "Gi-Shih Lien and Chen, {Chien Shu} and Wei-Yu Chen and Huang, {Shih Hao} and Kur-Ta Cheng and Chun-Mao Lin and Chao, {Su Hui}",
year = "2013",
month = "9",
doi = "10.1016/jjfda.2013.07.013",
language = "English",
volume = "21",
pages = "332--336",
journal = "Journal of Food and Drug Analysis",
issn = "1021-9498",
publisher = "Elsevier Taiwan LLC",
number = "3",

}

TY - JOUR

T1 - Photoproducts of Indomethacin exhibit decreased hydroxyl radical scavenging and xanthine oxidase inhibition activities

AU - Lien, Gi-Shih

AU - Chen, Chien Shu

AU - Chen, Wei-Yu

AU - Huang, Shih Hao

AU - Cheng, Kur-Ta

AU - Lin, Chun-Mao

AU - Chao, Su Hui

PY - 2013/9

Y1 - 2013/9

N2 - 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.

AB - 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.

KW - Electron spin resonance

KW - Hydroxyl radical

KW - Indomethacin

KW - Molecular modeling

KW - Photoproduct

KW - Xanthine oxidase

UR - http://www.scopus.com/inward/record.url?scp=84885673806&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84885673806&partnerID=8YFLogxK

U2 - 10.1016/jjfda.2013.07.013

DO - 10.1016/jjfda.2013.07.013

M3 - Article

AN - SCOPUS:84885673806

VL - 21

SP - 332

EP - 336

JO - Journal of Food and Drug Analysis

JF - Journal of Food and Drug Analysis

SN - 1021-9498

IS - 3

ER -