Synthesis, isolation and identification of glucuronides and mercapturic acids of a novel antiparasitic agent, licochalcone A

Abstract

1. Four glucuronic acidconjugates of licochalcone A(Lica),and their metabolites,have been synthesized using rabbit and pig liver microsomes and purified by preparative hplc. 2. The glucuronides were identified as E-Lica 4′-O-β-glucuronide, E and Z-Lica 4-O-β-glucuronide and a mono-glucuronide conjugate of a β-hydroxylated Lica metabolite. The metabolites were identified by hplc-nmr (one and two-dimensional nmr) as well as hplc-ms. 3. At pH 8·5 Lica reacted with N-acetyl-L-cysteine giving the twoepimeric conjugates, which were then isolated by preparative hplc and identified by one and two-dimensional nmr spectroscopic methods. 4. Only twoglucuronic acid conjugates (E- and Z-Lica 4-O-β-glucuronide) were found in the urine of rat after i.p. administration of a single dose of Lica.