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Planta Med 2009; 75(11): 1237-1240
DOI: 10.1055/s-0029-1185521
Pharmacology
Original Paper
© Georg Thieme Verlag KG Stuttgart · New York

Hydrophilic Ester-Bearing Chlorogenic Acid Binds to a Novel Domain to Inhibit Xanthine Oxidase

Shwu-Huey Wang1 , Chien-Shu Chen2 , Shih-Hao Huang3 , Szu-Hsu Yu1 , Zhi-Yang Lai4 , 6 , Sheng-Tung Huang5 , Chun-Mao Lin4 , 6
  • 1Graduate Institute of Medical Sciences, Taipei Medical University, Taipei, Taiwan
  • 2School of Pharmacy, China Medical University, Taichung, Taiwan
  • 3Department of Food Science, Taipei College of Maritime Technology, Taipei, Taiwan
  • 4School of Medicine, Taipei Medical University, Taipei, Taiwan
  • 5Institute of Biotechnology, National Taipei University of Technology, Taipei, Taiwan
  • 6Orthopedics Research Center, Taipei Medical University Hospital, Taipei, Taiwan
Further Information

Publication History

received Oct. 28, 2008 revised February 13, 2009

accepted February 25, 2009

Publication Date:
27 March 2009 (online)

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Abstract

Caffeic acid is a xanthine oxidase (XO) inhibitor that binds to the molybdopterin region of its active site. Caffeic acid phenethyl ester (CAPE) has higher hydrophobicity and exhibits stronger inhibition potency toward XO. Chlorogenic acid is a quinyl ester of caffeic acid that has increased hydrophilicity and also shows stronger XO inhibitory activity compared with caffeic acid. Caffeic acid and CAPE showed competitive inhibition against XO, whereas chlorogenic acid displayed mixed-type inhibition, implying that it binds to sites other than the active site. Structure-based molecular modeling was performed to account for the different binding characteristics of the hydrophobic and hydrophilic esters of caffeic acid. Chlorogenic acid showed weak binding to the molybdopterin region of XO, while it more strongly bound the flavin adenine dinucleotide region than it did the molybdopterin region. These results provide the basis for interactions of caffeic acid analogues with XO via various binding domains.

Key words

caffeic acid - chlorogenic acid - FAD - molecular modeling - molybdopterin - xanthine oxidase

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Dr. Chun-Mao Lin

College of Medicine,
Taipei Medical University

250 Wu-Hsing Street

Taipei 110

Taiwan

Phone: + 88 62 27 36 16 61 ext. 31 65

Fax: + 88 62 27 38 73 48

Email: cmlin@tmu.edu.tw

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