DMD Celsis microsomes equal better data

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

Drug Metabolism and Disposition Fast Forward
First published on November 15, 2007; DOI: 10.1124/dmd.107.018721

0090-9556/08/3602-461-468$20.00
DMD 36:461-468, 2008

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
dmd.107.018721v1
36/2/461    most recent
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Guo, J.
Right arrow Articles by van Breemen, R. B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Guo, J.
Right arrow Articles by van Breemen, R. B.

In Vitro Metabolism of Isoliquiritigenin by Human Liver Microsomes

Jian Guo, Dongting Liu, Dejan Nikolic, Dongwei Zhu, John M. Pezzuto, and Richard B. van Breemen

Department of Medicinal Chemistry and Pharmacognosy, University of Illinois College of Pharmacy, Chicago, Illinois (J.G., D.L., D.N., D.Z., R.B.v.B); and School of Pharmacy, University of Hawaii at Hilo, Hawaii (J.M.P.)

Isoliquiritigenin (2',4',4-trihydroxychalcone), a chalcone found in licorice root and other plants, has shown potent antitumor, antioxidant, and phytoestrogenic activity in vitro. In preparation for in vivo studies, the metabolism of isoliquiritigenin by human liver microsomes was investigated, and seven phase 1 metabolites were identified. In addition to aromatic hydroxylation that occurred on the A or B ring to form 2',4,4',5'-tetrahydroxychalcone or butein, respectively, reduction of the carbon-carbon double bond of an {alpha},β-unsaturated ketone and cyclization occurred to form 2',4,4'-trihydroxydihydrochalcone and (Z/E)-6,4'-dihydroxyaurone. All metabolites were characterized and identified by using liquid chromatography-tandem mass spectrometry with comparison to authenticated compounds. Finally, monoclonal antibody inhibitors of specific human cytochrome P450 (P450) enzymes and recombinant human P450 enzymes were used to identify the enzymes responsible for the formation of the major mono-oxygenated metabolites, and P450 2C19 was found to be a significant enzyme in the formation of butein from isoliquiritigenin, which also has anticancer activity. Cytochromes P450, reactive oxygen species, and peroxidases can all contribute to the formation of (Z/E)-6,4'-dihydroxyaurone in human liver microsomes.

Address correspondence to: Dr. Richard B. van Breemen, Department of Medicinal Chemistry and Pharmacognosy, University of Illinois College of Pharmacy, 833 S. Wood St., Chicago, IL 60612-7231. E-mail: breemen{at}uic.edu.




This article has been cited by other articles:


Home page
 Drug Metab. Dispos.Home page
J. Guo, A. Liu, H. Cao, Y. Luo, J. M. Pezzuto, and R. B. van Breemen
Biotransformation of the Chemopreventive Agent 2',4',4-Trihydroxychalcone (Isoliquiritigenin) by UDP-Glucuronosyltransferases
Drug Metab. Dispos., October 1, 2008; 36(10): 2104 - 2112.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 2008 by the American Society for Pharmacology and Experimental Therapeutics.