Wedelolactone metabolism in rats through regioselective glucuronidation catalyzed by uridine diphosphate-glucuronosyltransferases 1As (UGT1As) was written by Li, Liang;Huang, Xue-juan;Peng, Jian-long;Zheng, Ming-yue;Zhong, Da-fang;Zhang, Chao-feng;Chen, Xiao-yan. And the article was included in Phytomedicine in 2016.Recommanded Product: 1,8,9-Trihydroxy-3-methoxy-6H-benzofuro[3,2-c]chromen-6-one The following contents are mentioned in the article:
Wedelolactone (WEL), a medicinal plant-derived coumestan, has been reported to exhibit a diverse range of pharmacol. activities. However, the metabolism and disposition of WEL remain unexplored.The present study aims to investigate the metabolism of WEL in rats and identify the enzymes responsible for forming major WEL metabolites.Plasma, urine, feces, and bile samples were collected before and after 50 mg/kg WEL was orally administered to rats. Metabolites were profiled by ultrahigh performance liquid chromatog./quadrupole time-of-flight mass spectrometry and identified by high-performance liquid chromatog.-solid-phase extraction-NMR spectroscopy. The in vitro WEL glucuronidation activities of human liver microsomes, human kidney microsomes, human intestine microsomes, and 12 recombinant human uridine diphosphate-glucuronosyltransferase (UGT) isoforms were screened. Mol. docking simulation of the interaction between WEL and UGT1A9 was conducted.WEL underwent extensive metabolism, and 17 metabolites were identified. The major metabolic pathways observed were glucuronidation and methylation. Glucuronic acid was preferentially introduced into 5-OH, whereas no obvious regioselectivity was observed in the methylation of 11-OH and 12-OH. Multiple UGTs, including UGT1A1, UGT1A3, UGT1A6, UGT1A7, UGT1A8, UGT1A9, and UGT1A10, were involved in forming WEL glucuronides and O-methylated WEL glucuronides.The extensive glucuronidation and methylation is responsible for the low oral bioavailability of WEL in rats. UGT1A1 and UGT1A9 were the major enzymes involved in the glucuronidation of WEL and O-methylated WEL. Mol. docking studies revealed that 5-OH was accessible to the catalytic domain of UGT1As; therefore, 5-OH exhibited a high probability of glucuronidation. This study involved multiple reactions and reactants, such as 1,8,9-Trihydroxy-3-methoxy-6H-benzofuro[3,2-c]chromen-6-one (cas: 524-12-9Recommanded Product: 1,8,9-Trihydroxy-3-methoxy-6H-benzofuro[3,2-c]chromen-6-one).
1,8,9-Trihydroxy-3-methoxy-6H-benzofuro[3,2-c]chromen-6-one (cas: 524-12-9) belongs to benzofurans derivatives.Benzofuran is one of the most significant oxygen-containing heterocycles consisting of fused benzene and furan ring, which are widely presented in various naturally occurring and synthetically active compounds. Benzofurans are stable towards alkali and readily polymerize on treatment with sulfuric acid, due to which they are useful for the preparation of low cost chemically relatively inert resins.Recommanded Product: 1,8,9-Trihydroxy-3-methoxy-6H-benzofuro[3,2-c]chromen-6-one
Referemce:
Benzofuran – Wikipedia,
Benzofuran | C8H6O – PubChem