In Vitro Glycosidation Potential Towards Olomoucine-Type
Cyclin-Dependent Kinase Inhibitors in Rodent and Primate
Microsomes
K. ČERVENKOVÁ1,
M. BELEJOVÁ2, Z. CHMELA1, M. RYPKA1,
D. RIEGROVÁ1, K. MICHNOVÁ1, K.
MICHALÍKOVÁ1, I. ŠÚROVÁ3, A. BREJCHA3,
J. HANUŠ4, B. ČERNÝ5, K. FUKSOVÁ5,
L. HAVLÍČEK4, J. VESELÝ1
1Department of Pathological Physiology, 2Department
of Pharmacology, Medical Faculty, Palacký University,
Olomouc, 3BioTest, Pardubice, 4Institute
of Experimental Botany, Academy of Sciences, Prague and
5Institute of Nuclear Medicine, First Faculty
of Medicine, Charles University, Prague, Czech Republic
Received
January 16, 2002
Accepted August 27, 2002
Summary
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 3H-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.
Key
words
Glycosidation • Mouse • Rat • Monkey • Human • CDK inhibitors
Reprint
requests
Doc. MUDr. Jaroslav Veselý, CSc., Department of Pathological
Physiology, Medical Faculty, Palacký University, Hněvotínská 3,
CZ-775 15 Olomouc, Czech Republic. E-mail:
vesely@tunw.upol.cz
|
