31528-44-6Relevant articles and documents
Preparative Enzymatic Synthesis of the Acylglucuronide of Mycophenolic Acid
Kittelmann, Matthias,Rheinegger, Urs,Espigat, Aude,Oberer, Lukas,Aichholz, Reiner,Francotte, Eric,Ghisalba, Oreste
, p. 825 - 829 (2003)
The acylglucuronide (3) of mycophenolic acid (1) was enzymatically synthesised on a preparative scale (450 mg substrate) under optimised reaction conditions with 51% conversion. By screening 9 liver homogenates from 8 vertebrate species, it was shown that only with liver homogenate from horse as the catalyst were the acyl- (3) and the O-glucuronide (2) were formed in a ca. 1:1 ratio. With homogenates from other sources, the O-glucuronide (2) was produced in high excess. By optimising the concentration of the co-substrate UDP-glucuronic acid and the reaction temperature, the conversion to the acylglucuronide (3) was increased from initially 34 to 55% and the ratio of acyl- (3) to O-glucuronide (2) from 1.5:1 to 3.9:1. The reaction was also performed continuously in an enzyme membrane reactor, however, with lower conversion yield and therefore, higher specific UDP-glucuronic acid consumption.
Inhibition of intestinal and hepatic glucuronidation of mycophenolic acid by Ginkgo biloba extract and flavonoids
Mohamed, Mohamed-Eslam F.,Frye, Reginald F.
, p. 270 - 275 (2010)
Herb-drug interactions have received more attention in recent years because of the widespread popularity of herbal supplements. However, there are limited data on the effect of herbs on glucuronidation in humans. The goal of this work was to examine the effect of Ginkgo biloba extract and its main flavonoid and terpene lactone constituents on mycophenolic acid (MPA) 7-Oglucuronidation. Human liver (HLM) and intestinal (HIM) microsomes were incubated with MPA and G. biloba extract (unhydrolyzed or acid-hydrolyzed), quercetin, kaempferol, ginkgolide A, ginkgolide B, or bilobalide. MPA-7-O-glucuronide formation was inhibited in HLM and HIM incubations by unhydrolyzed [IC50 = 84.3 (HLM) and 6.9 (HIM) μg/ml] and hydrolyzed [IC50 = 20.9 (HLM) and 4.3 (HIM) μg/ml] G. biloba extracts, quercetin [IC50 = 19.1 (HLM) and 5.8 (HIM) μM], and kaempferol [IC50 = 23.1 (HLM) and 7.7 (HIM) μM]. Terpene lactones did not show inhibition of MPA glucuronidation. Quercetin was a mixed-type inhibitor in HLM and HIM incubations [Ki = 11.3 (HLM) and 2.8 (HLM) μM], whereas kaempferol was a noncompetitive inhibitor in HLM (Ki = 33.7 μM) and a mixed-type inhibitor in HIM (Ki = 4.5 μM). These results indicate that G. biloba extract or quercetin-and kaempferol-rich supplements may inhibit intestinal and hepatic glucuronidation of MPA. Future studies are needed to evaluate the clinical significance of this interaction. Copyright
Convenient syntheses of the in vivo carbohydrate metabolites of mycophenolic acid: reactivity of the acyl glucuronide
Jones, Amy E.,Wilson, Helen K.,Meath, Paul,Meng, Xiaoli,Holt, David W.,Johnston, Atholl,Oellerich, Michael,Armstrong, Victor W.,Stachulski, Andrew V.
supporting information; experimental part, p. 4973 - 4977 (2009/12/05)
Following in vivo use of mycophenolic acid, the O-aryl and O-acyl glucuronides, as well as the recently discovered O-aryl glucoside (Scheme 1), are all found as metabolites. We describe convenient preparations of all three derivatives. The phenolic glycos
