0172271 - UEB-Q 20023056 RIV GB eng J - Journal Article
Rypka, M. - Veselý, J. - Chmela, Z. - Riegrová, D. - Červenková, K. - Havlíček, Libor - Lemr, K. - Hanuš, Jan - Černý, B. - Lukeš, J. - Michalíková, K.
In vitro biotransformation of 2,6,9-trisubstituted purine-derived cyclin-dependent kinase inhibitor bohemine by mouse liver microsomes.
Xenobiotica. Roč. 32, č. 11 (2002), s. 1017-1031. ISSN 0049-8254. E-ISSN 1366-5928
R&D Projects: GA MŠMT OC 844.10; GA ČR GA301/02/0475
Institutional research plan: CEZ:AV0Z5038910
Keywords : CYTOCHROME P450 INHIBITORS * METABOLIC ACTIVATION * ANTICANCER
Subject RIV: CE - Biochemistry
Impact factor: 1.919, year: 2002

Biotransformation pathways of the cyclin-dependent kinase inhibitor 6-benzylamino-2-(3-hydroxypropylamino)-9-isopropylpurine (bohemine) by mouse liver microsomes in vitro were investigated. 2. Metabolite profiles of [8-3H]-labelled bohemine were established by TLC/3H-autoradiography and enzymatic and MS analyses were used to elucidate the chemical structures of the metabolites. The structures of the main primary metabolites were confirmed by synthesis of authentic compounds. 3. A schema of the primary NADPH-dependent pathways has been proposed involving N2- and N9-dealkylation, N6-debenzylation, aromatic hydroxylation, and C2 side chain oxidation of bohemine. Three of the primary metabolites detected, 6-(benzylamino)-2-(3-hydroxypropylamino)purine (M4), 6-amino-2-(3-hydroxypropylamino)-9-isopropylpurine (M5) and 6-(4-hydroxybenzylamino)-2-(3-hydroxypropylamino)-9-isopropylpurine (M6), all retaining their parent primary hydroxyl group, were subsequently shown to be converted, by a liver cytosolic NAD+-dependent system, into their corresponding carboxylic acids.
Permanent Link: http://hdl.handle.net/11104/0069310