RT Journal Article SR Electronic T1 Chemoenzymatic Preparation of Silybin β-Glucuronides and Their Biological Evaluation JF Drug Metabolism and Disposition JO Drug Metab Dispos FD American Society for Pharmacology and Experimental Therapeutics SP 1513 OP 1517 VO 28 IS 12 A1 Vladimír Kr̆en A1 Jitka Ulrichová A1 Pavel Kosina A1 David Stevenson A1 Petr Sedmera A1 Věra Přikrylová A1 Petr Halada A1 Vilím šsimánek YR 2000 UL http://dmd.aspetjournals.org/content/28/12/1513.abstract AB Chemoenzymatic glucuronidation of the optically pure silybin A (1) using ovine liver glucuronyl transferase afforded three β-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-β-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 theo-methoxy-phenolic structure at C-19, C-20. This is first pharmacological study using optically pure silybin. The American Society for Pharmacology and Experimental Therapeutics