Chemoenzymatic preparation of silybin beta-glucuronides and their biological evaluation
Jazyk angličtina Země Nizozemsko Médium print
Typ dokumentu klinické zkoušky, časopisecké články, práce podpořená grantem
PubMed
11095591
Knihovny.cz E-zdroje
- MeSH
- glukuronidy krev chemie farmakologie MeSH
- glukuronosyltransferasa metabolismus MeSH
- lidé MeSH
- magnetická rezonanční spektroskopie MeSH
- scavengery volných radikálů krev chemie farmakologie MeSH
- silymarin krev chemie farmakologie MeSH
- stereoizomerie MeSH
- vysokoúčinná kapalinová chromatografie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky MeSH
- práce podpořená grantem MeSH
- Názvy látek
- glukuronidy MeSH
- glukuronosyltransferasa MeSH
- scavengery volných radikálů MeSH
- silymarin MeSH
Chemoenzymatic glucuronidation of the optically pure silybin A (1) using ovine liver glucuronyl transferase afforded three beta-glucuronides of silybin, substituted at phenolic OH groups at the positions C-20 (2), C-7 (3), and C-5 (4) formed in the yields 27, 62.5, and 2.5%, respectively. Using these standards, it was shown that the main silybin conjugate in humans is its 20-beta-D-glucuronate (2), while the C-7 regioisomer (3) was formed in lower proportion. The rate of conjugation of (natural) silybin diastereomers 10S, 11S and 10R, 11R, and therefore also their metabolism in humans is rather different. The radical scavenging activity of 2 is considerably lower than that of its aglycone (1); however, the activity of 3 is higher than in the silybin. These findings corroborate the hypothesis that, at physiological pH, the exclusive target for one-electron oxidation of the silybin molecule is the o-methoxy-phenolic structure at C-19, C-20. This is first pharmacological study using optically pure silybin.
Chirality Matters: Biological Activity of Optically Pure Silybin and Its Congeners
Sulfated Metabolites of Flavonolignans and 2,3-Dehydroflavonolignans: Preparation and Properties
Compounds isolated at the Institute of Microbiology in 1989-2001 and future trends