Biotransformation of the chemopreventive agent 2',4',4-trihydroxychalcone (isoliquiritigenin) by UDP-glucuronosyltransferases.

Biotransformation of the chemopreventive agent 2',4',4-trihydroxychalcone (isoliquiritigenin) by UDP-glucuronosyltransferases. Research Abstract Details 

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Biotransformation of the chemopreventive agent 2',4',4-trihydroxychalcone (isoliquiritigenin) by UDP-glucuronosyltransferases. Abstract Text:

2',4',4-trihydroxychalcone (isoliquiritigenin), a chalcone found in licorice root and shallots, exhibits antioxidant, estrogenic, and antitumor activities. To complement our previous studies concerning the phase 1 metabolism of isoliquiritigenin, the phase 2 transformation of isoliquiritigenin by human hepatocytes and pooled human liver microsomes (HLMs) was investigated using liquid chromatography/tandem mass spectrometry and UV absorbance. Five glucuronides were detected corresponding to monoglucuronides of isoliquiritigenin and liquiritigenin, but no sulfate conjugates were observed. The UDP-glucuronosyltransferases (UGTs) involved in the formation of the major glucuronide conjugates were identified using recombinant human UGTs in combination with liquid chromatography/mass spectrometry. UGT1A1 and UGT1A9 were the major enzymes responsible for the formation of the most abundant conjugate, isoliquiritigenin 4'-O-glucuronide (MG5), with Km values of 4.30+/-0.47 and 3.15+/-0.24 microM, respectively. UGT1A1 and UGT1A10 converted isoliquiritigenin to the next most abundant phase 2 metabolite, isoliquiritigenin 2'-O-glucuronide (MG4), with Km values of 2.98+/-0.8 and 25.8+/-1.3 microM, respectively. In addition, isoliquiritigenin glucuronides MG4 and MG5 were formed by pooled human intestine and kidney microsomes, respectively. Based on the in vitro determination of a 25.3-min half-life for isoliquiritigenin when incubated with HLMs, the intrinsic clearance of isoliquiritigenin was estimated to be 36.4 ml/min/kg. These studies indicate that isoliquiritigenin will be conjugated rapidly in the liver to form up to five monoglucuronides.

Biotransformation of the chemopreventive agent 2',4',4-trihydroxychalcone (isoliquiritigenin) by UDP-glucuronosyltransferases. Publishing Authors By Initials

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Biotransformation of the chemopreventive agent 2',4',4-trihydroxychalcone (isoliquiritigenin) by UDP-glucuronosyltransferases. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Drug metabolism and disposition: the biological fa

VOLUME: 36

Page Numbers: 2104-12

Journal Abbreviation: Drug Metab. Dispos.

ISSN: 1521-009X

DAY: 24

MONTH: 07

YEAR: 2008

Biotransformation of the chemopreventive agent 2',4',4-trihydroxychalcone (isoliquiritigenin) by UDP-glucuronosyltransferases. Information

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LANGUAGE: eng

NlmUniqueID: 9421550

Biotransformation of the chemopreventive agent 2',4',4-trihydroxychalcone (isoliquiritigenin) by UDP-glucuronosyltransferases. Keywords Mesh Terms:

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Chemical & Substance for Abstract: Biotransformation of the chemopreventive agent 2',4',4-trihydroxychalcone (isoliquiritigenin) by UDP-glucuronosyltransferases. Information

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Grant and Affiliation Information for Biotransformation of the chemopreventive agent 2',4',4-trihydroxychalcone (isoliquiritigenin) by UDP-glucuronosyltransferases.

AFFILIATION: Department of Medicinal Chemistry and Pharmacognosy, University of Illinois College of Pharmacy, 833 S. Wood St., Chicago, IL 60612-7231, USA.

Country: United States

AGENCY: United States NCI

GRANT: P01 CA48112

ACRONYM: CA

MEDLINETA: Drug Metab Dispos

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