In vivo metabolism of 2,6,9-trisubstituted purine-derived cyclin-dependent kinase inhibitor bohemine in mice: glucosidation as the principal metabolic route

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15310%2F01%3A00001295" target="_blank" >RIV/61989592:15310/01:00001295 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61389030:_____/01:56013064 RIV/61989592:15110/01:00000393

Výsledek na webu

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DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

In vivo metabolism of 2,6,9-trisubstituted purine-derived cyclin-dependent kinase inhibitor bohemine in mice: glucosidation as the principal metabolic route

Popis výsledku v původním jazyce

Synthetic cyclin-dependent kinase inhibitors have recently been referred to as effective antiproliferative agents. This study was conducted to characterize clearance of a 3H-labeled, trisubstituted purine-type inhibitor, 8-[3H]bohemine [6-benzylamino-2-(3-hydroxypropylamino)-9-isopropylpurine], in mice. Radioactivity profiles were analyzed by liquid scintillation counting and by thin layer chromatography followed by autoradiography. Metabolite structures were elucidated by mass spectrometry, NMR, and enzymatic analyses. Bohemine was rapidly and completely metabolized in vivo and disappeared from circulation during the first 60 min following intravenous administration. The metabolites were partly eliminated by the hepatobiliary tract and partly by renalexcretion. The terminal hydroxyl group located at the C2 side chain of bohemine made the compound susceptible to main metabolic attacks, i.e., distinct types of conjugation reactions with glycosyl donors as well as an oxidative reaction.

Název v anglickém jazyce

In vivo metabolism of 2,6,9-trisubstituted purine-derived cyclin-dependent kinase inhibitor bohemine in mice: glucosidation as the principal metabolic route

Popis výsledku anglicky

Synthetic cyclin-dependent kinase inhibitors have recently been referred to as effective antiproliferative agents. This study was conducted to characterize clearance of a 3H-labeled, trisubstituted purine-type inhibitor, 8-[3H]bohemine [6-benzylamino-2-(3-hydroxypropylamino)-9-isopropylpurine], in mice. Radioactivity profiles were analyzed by liquid scintillation counting and by thin layer chromatography followed by autoradiography. Metabolite structures were elucidated by mass spectrometry, NMR, and enzymatic analyses. Bohemine was rapidly and completely metabolized in vivo and disappeared from circulation during the first 60 min following intravenous administration. The metabolites were partly eliminated by the hepatobiliary tract and partly by renalexcretion. The terminal hydroxyl group located at the C2 side chain of bohemine made the compound susceptible to main metabolic attacks, i.e., distinct types of conjugation reactions with glycosyl donors as well as an oxidative reaction.

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

ED - Fyziologie

OECD FORD obor

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Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

Z - Vyzkumny zamer (s odkazem do CEZ)

Rok uplatnění

2001

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Drug Metabolism and Disposition

ISSN

0090-9556

e-ISSN

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Svazek periodika

3

Číslo periodika v rámci svazku

29

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

9

Strana od-do

326-334

Kód UT WoS článku

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EID výsledku v databázi Scopus

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