The chemistry and biological activity of acyl glucuronides.
The role of acyl glucuronides (AGs) as metabolites of carboxylic acids has been known for over 60 years, but their potential as reactive or potentially toxic metabolites is still a matter of debate. While recent advances in analytical techniques have demonstrated convincingly that AGs can interact with proteins in vivo, the consequences of these interactions are still unclear. In this review, following an introduction to the biosynthesis and basic chemical reactivity of AGs, recent important developments in the analytical detection and synthesis of AGs are presented. The chemical and biological reactivity of AGs are then discussed, and recent case studies of carboxylic acid therapeutics spanning a range of therapeutic areas are tabulated.
Stachulski
Andrew V
AV
Robert Robinson Laboratories, Department of Chemistry, University of Liverpool, Liverpool, L69 7ZD, UK. stachuls@liv.ac.uk
D000215:Acylation; D000818:Animals; D002264:Carboxylic Acids / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use*; D020719:Glucuronides / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008956:Models, Chemical; D015394:Molecular Structure; D047493:PPAR alpha / Q000819:agonists; D047495:PPAR gamma / Q000819:agonists
D002264:Carboxylic Acids; D020719:Glucuronides; D047493:PPAR alpha; D047495:PPAR gamma