Structure-activity relationship of C6-C3 phenylpropanoids on xanthine oxidase-inhibiting and free radical-scavenging activities

Yuan Ching Chang, Fu Wei Lee, Chien Shu Chen, Sheng Tung Huang, Shin Hui Tsai, Shih Hao Huang, Chun Mao Lin

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

We employed the techniques of DNA relaxation, DPPH (1,1-diphenyl-2-picrylhydrazyl hydrate), and DMPO (5,5-dimethyl-1-pyrroline-N-oxide)-electron spin resonance (ESR), to study the effects of reactive oxygen species (ROS) suppression by 11 selected C6-C3 phenylpropanoid derivatives under oxidative conditions. We also investigated the effects of the derivatives on the inhibition of xanthine oxidase (XO) activity, and the structure-activity relationships (SARs) of these derivatives against XO activity were further examined using computer-aided molecular modeling. Caffeic acid was the most potent radical scavenger among the 11 test compounds. Our results suggest that the chemical structure and number of hydroxyl groups on the benzene ring of phenylpropanoids are correlated with the effects of ROS suppression. All test derivatives were competitive inhibitors of XO. The results of the structure-based molecular modeling exhibited interactions between phenylpropanoid derivatives and the molybdopterin region of XO. The para-hydroxyl of phenylpropanoid derivatives was pointed toward the guanidinium group of Arg 880. The phenylpropanoid derivatives containing the meta-or ortho-hydroxyl formed hydrogen bonds with Thr 1010. In addition, meta-hydroxyl formed hydrogen bonds with the peptide bond between the residues of Thr1010 and Phe1009. CAPE, the phenylenethyl ester of phenylpropanoids, had the highest affinity toward the binding site of XO, and we speculated that this was due to hydrophobic interactions of the phenylethyl ester with several hydrophobic residues surrounding the active site. The hypoxanthine/XO reaction in the DMPO-ESR technique was used to correlate the effects of these phenylpropanoid derivatives on enzyme inhibition and ROS suppression, and the results showed that caffeic acid and CAPE were the two most potent agents among the tested compounds. We further assessed the effects of the test compounds on living cells, and CAPE was the most potent agent for protecting cells against ROS-mediated damage among the tested phenylpropanoids.

Original languageEnglish
Pages (from-to)1541-1551
Number of pages11
JournalFree Radical Biology and Medicine
Volume43
Issue number11
DOIs
Publication statusPublished - Dec 1 2007

Fingerprint

Xanthine Oxidase
Scavenging
Structure-Activity Relationship
Free Radicals
Derivatives
Hydroxyl Radical
Reactive Oxygen Species
Paramagnetic resonance
Molecular modeling
Hydrogen
Esters
Molecular Computers
Relaxation Therapy
Hydrogen bonds
Guanidine
Electron Spin Resonance Spectroscopy
Benzene
Molecular Structure
Hydrophobic and Hydrophilic Interactions
Enzyme inhibition

Keywords

  • Caffeic acid
  • CAPE
  • Molecular modeling
  • Phenylpropanoid
  • ROS
  • Xanthine oxidase

ASJC Scopus subject areas

  • Medicine(all)
  • Toxicology
  • Clinical Biochemistry

Cite this

Structure-activity relationship of C6-C3 phenylpropanoids on xanthine oxidase-inhibiting and free radical-scavenging activities. / Chang, Yuan Ching; Lee, Fu Wei; Chen, Chien Shu; Huang, Sheng Tung; Tsai, Shin Hui; Huang, Shih Hao; Lin, Chun Mao.

In: Free Radical Biology and Medicine, Vol. 43, No. 11, 01.12.2007, p. 1541-1551.

Research output: Contribution to journalArticle

Chang, Yuan Ching ; Lee, Fu Wei ; Chen, Chien Shu ; Huang, Sheng Tung ; Tsai, Shin Hui ; Huang, Shih Hao ; Lin, Chun Mao. / Structure-activity relationship of C6-C3 phenylpropanoids on xanthine oxidase-inhibiting and free radical-scavenging activities. In: Free Radical Biology and Medicine. 2007 ; Vol. 43, No. 11. pp. 1541-1551.
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AU - Tsai, Shin Hui

AU - Huang, Shih Hao

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