title: In vitro glycosidation potential towards olomoucine-type cyclin-dependent kinase inhibitors in rodent and primate microsomes.
abstract: Interspecies differences in glycosidation potential in mammalian tissues represent a factor contributing to ambiguity when endobiotic and/or xenobiotic metabolic pathways are extrapolated from animals to man. Using the TLC/autoradiographic technique, we conducted an in vitro investigation involving mouse, rat, monkey, as well as human liver and kidney microsomes to evaluate their glycoconjugation potential towards (3)H-labeled, purine-derived selective inhibitors of cyclin-dependent kinases such as olomoucine, bohemine, roscovitine, 6-(2-hydroxybenzyl)amino-2-(1-hydroxymethyl-2-methylpropyl)amino-9-isopropylpurine (compound A-4), and 6-(3-hydroxybenzyl)amino-2-[(1(R/S)-hydroxymethyl)propyl]amino-9-isopropylpurine (compound A-5) as aglycones. Principally, this study confirmed the aliphatic hydroxyl group of olomoucine-type inhibitors as a relatively suitable target for glucuronide, glucoside, xyloside, galactoside, and/or N-acetylaminoglucoside conjugation. Of the tissues examined, only the mouse microsomes were able to perform glucosidation and galactosidation reactions with the aglycones. On the other hand, monkey microsomes were superior to the mouse microsomes in a variety of glucuronide conjugates produced with compounds A-4 and A-5.
authors.affiliation: Department of Pathological Physiology, Medical Faculty, Palacký University, Hnevotínská 3, CZ-775 15 Olomouc, Czech Republic. vesely@tunw.upol.cz
authors.forename: K
authors.initials: K
authors.lastname: Cervenková
authors.forename: M
authors.initials: M
authors.lastname: Belejová
authors.forename: Z
authors.initials: Z
authors.lastname: Chmela
authors.forename: M
authors.initials: M
authors.lastname: Rypka
authors.forename: D
authors.initials: D
authors.lastname: Riegrová
authors.forename: K
authors.initials: K
authors.lastname: Michnová
authors.forename: K
authors.initials: K
authors.lastname: Michalíková
authors.forename: I
authors.initials: I
authors.lastname: Súrová
authors.forename: A
authors.initials: A
authors.lastname: Brejcha
authors.forename: J
authors.initials: J
authors.lastname: Hanus
authors.forename: B
authors.initials: B
authors.lastname: Cerný
authors.forename: K
authors.initials: K
authors.lastname: Fuksová
authors.forename: L
authors.initials: L
authors.lastname: Havlícek
authors.forename: J
authors.initials: J
authors.lastname: Veselý
mesh_terms: D000818:Animals; D002855:Chromatography, Thin Layer; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D006027:Glycosides / Q000378:metabolism*; D006031:Glycosylation; D006801:Humans; D066298:In Vitro Techniques; D007668:Kidney / Q000378:metabolism; D007701:Kinetin; D008253:Macaca mulatta; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D051379:Mice; D008861:Microsomes / Q000187:drug effects / Q000201:enzymology*; D008862:Microsomes, Liver / Q000378:metabolism; D011687:Purines / Q000138:chemical synthesis / Q000494:pharmacology*; D051381:Rats; D013045:Species Specificity
chemical_list: D004791:Enzyme Inhibitors; D006027:Glycosides; D011687:Purines; C090046:olomoucine; D018844:Cyclin-Dependent Kinases; D007701:Kinetin