Biotransformation of the Chemopreventive Agent 2,4,4-Trihydroxychalcone (Isoliquiritigenin) by UDP-Glucuronosyltransferases

2,4,4-Trihydroxychalcone (isoliquiritigenin), a chalcone found in licorice root and shallots, exhibits antioxidant, estrogenic, and antitumor activities. To complement our previous studies concern-ing the phase 1 metabolism of isoliquiritigenin, the phase 2 trans-formation 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 monogluc-uronides of isoliquiritigenin and liquiritigenin, but no sulfate con-jugates 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), wit