Synthesis, isolation and identification of glucuronides and mercapturic acids of a novel antiparasitic agent, licochalcone A.
1. Four glucuronic acid conjugates 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-beta-glucuronide, E and Z-Lica 4-O-beta-glucuronide and a mono-glucuronide conjugate of a beta-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 two epimeric conjugates, which were then isolated by preparative hplc and identified by one and two-dimensional nmr spectroscopic methods. 4. Only two glucuronic acid conjugates (E- and Z-Lica 4-O-beta-glucuronide) were found in the urine of rat after i.p. administration of a single dose of Lica.
Nadelmann
L
L
Department of Analytical and Pharmaceutical Chemistry, Royal Danish School of Pharmacy, Copenhagen, Denmark.
Tjørnelund
J
J
Hansen
S H
SH
Cornett
C
C
Sidelmann
U G
UG
Braumann
U
U
Christensen
E
E
Christensen
S B
SB
D000111:Acetylcysteine / Q000032:analysis / Q000302:isolation & purification / Q000378:metabolism*; D000818:Animals; D000981:Antiprotozoal Agents / Q000032:analysis / Q000302:isolation & purification / Q000378:metabolism*; D002599:Chalcone / Q000031:analogs & derivatives* / Q000032:analysis / Q000302:isolation & purification / Q000378:metabolism; D047188:Chalcones; D002851:Chromatography, High Pressure Liquid; D005260:Female; D016166:Free Radical Scavengers; D005965:Glucuronates / Q000032:analysis / Q000302:isolation & purification / Q000378:metabolism*; D007274:Injections, Intraperitoneal; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D013552:Swine / Q000378:metabolism
D000981:Antiprotozoal Agents; D047188:Chalcones; D016166:Free Radical Scavengers; D005965:Glucuronates; D002599:Chalcone; C070840:licochalcone A; D000111:Acetylcysteine