Abstract
Hyperuricemia is a condition where high level of uric acid is present in the blood. One of the factors contributing to this is the overproduction of uric acid by hydroxylation of xanthine which is catalyzed by Xanthine Oxidase (XO). Flavonoids have been shown to possess high activity for inhibition toward xanthine oxidase, and found to have the ability to decrease uric acid levels in serum. In this study, we perform molecular docking for more than 100 natural flavonoids onto XO, using Auto Dock 3.0.5 software. The result showed that ErysubinF, an isoflavone, has a superior inhibition activity compared to others flavonoids with a very low docked energy (docked energy = −12.82 Kcal/mol). Analysis using both Ligplot and InsightII showed that the main interaction between ErysubinF and the enzyme’s active site involves only hydrophobic interaction due to the presence of two isopentene side chains.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Nakagawa, T., et al., Uric acid-A uremic toxin? Blood Purification, 2006. 24(1): p. 67.
Schlesinger, N. and H.R. Schumacher Jr, Update on gout. Arthritis and Rheumatism, 2002. 47(5): p. 563.
Fields, M., C.G. Lewis, and M.D. Lure, Allopurinol, an inhibitor of xanthine oxidase, reduces uric acid levels and modifies the signs associated with copper deficiency in rats fed fructose. Free Radical Biology and Medicine, 1996. 20(4): p. 595.
Horiuchi, H., et al., Allopurinol induces renal toxicity by impairing pyrimidine metabolism in mice. Life Sciences, 2000. 66(21): p. 2051.
Borges, F., E. Fernande, and F. Roleira, Progress towards the discovery of xanthine oxidase inhibitors. Current Medicinal Chemistry, 2002. 9(2): p. 195.
Wright, J.D. and A.B. Pinto, Clinical manifestations and treatment of gout. Primary Care Update for Ob/Gyns, 2003. 10(1): p. 19.
Weselman, K.O. and C.A. Agudelo, Gout basics. Bulletin on the Rheumatic Diseases, 2001. 50(9): p. 1.
Hille, R., The mononuclear molybdenum enzymes. Chemical Reviews, 1996. 96(7): p. 2757.
Kisker, C., et al., A structural comparison of molybdenum cofactorcontaining. enzymes. FEMS Microbiology Reviews, 1998. 22(5): p. 503.
Mondal, M.S., A.K. Sau, and S. Mitra, Mechanism of the inhibition of milk xanthine oxidase activity by metal ions: a transient kinetic study. 2000. 1480(1–2): p. 302.
Enroth, C., et al., Crystal structures of bovinemilk xanthine dehydrogenase and xanthine oxidase: Structure-based mechanism of conversion. Proceedings of the National Academy of Sciences of the United States of America, 2000. 97(20): p. 10723.
Nishino, T., The conversion of xanthine dehydrogenase to xanthine oxidase and the role of the enzyme in reperfusion injury. Journal of Biochemistry, 1994. 116(1): p. 1.
Godber, B.L.J., et al., Molecular characterization of human xanthine oxidoreductase: The enzyme is grossly deficient in molybdenum and substantially deficient in iron-sulphur centres. Biochemical Journal, 2005. 388(2): p. 501.
Abdeh, S., et al., Purification and partial characterization of xanthine oxidase from human milk. Biochimica et Biophysica Acta-General Subjects, 1992. 1117(1): p. 25.
Lin, C.M., et al., Molecular modeling of flavonoids that inhibits xanthine oxidase. Biochemical and Biophysical Research Communications, 2002. 294(1): p. 167.
Cos, P., et al., Structure-activity relationship and classification of flavonoids as inhibitors of xanthine oxidase and superoxide scavengers. Journal of Natural Products, 1998. 61(1): p. 71.
Farkas, O., J. Jakus, and K. He?berger, Quantitative structure-Antioxidant activity relationships of flavonoid compounds. Molecules, 2004. 9(12): p. 1079.
Hyperchem, Hypercube, Inc. 1115 NW 4th street Gainesville, Florida 32601, USA. Release 7.5, 2002.
Author information
Authors and Affiliations
Corresponding author
Editor information
Rights and permissions
Copyright information
© 2007 International Federation for Medical and Biological Engineering
About this paper
Cite this paper
Omar, B., Mohamed, N., Rahim, R.A., Wahab, H.A. (2007). Natural Flavonoids for the treatment of Hyperuricemia, Molecular Docking studies. In: Magjarevic, R., Nagel, J.H. (eds) World Congress on Medical Physics and Biomedical Engineering 2006. IFMBE Proceedings, vol 14. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-36841-0_53
Download citation
DOI: https://doi.org/10.1007/978-3-540-36841-0_53
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-540-36839-7
Online ISBN: 978-3-540-36841-0
eBook Packages: EngineeringEngineering (R0)