9-Norbornyl-6-chloropurine Is a Novel Antileukemic Compound Interacting with Cellular GSH

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F13%3A00396057" target="_blank" >RIV/61388963:_____/13:00396057 - isvavai.cz</a>

Result on the web

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DOI - Digital Object Identifier

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Result language

angličtina

Original language name

9-Norbornyl-6-chloropurine Is a Novel Antileukemic Compound Interacting with Cellular GSH

Original language description

Aim: 6-Chloropurines substituted at position 9 with bicyclic skeletons represent promising chemotherapeutic agents. We explored the metabolism and membrane transport of 9-norbornyl-6-chloropurine (NCP) aiming to understand its mechanism of action. Materials and Methods: The metabolism of NCP was studied in vitro in whole cells (CCRF-CEM), cellular extracts, subcellular fractions and purified enzymes. Transport experiments were conducted in Caco-2 cell monolayers. Results: Three metabolites were identified, a glutathione conjugate (NCP-GS), NCP-cysteinylglycine and NCP-cysteine. Both glutathione-S-transferase inhibition and glutathione (GSH) depletion prevented metabolite formation and increased the cytotoxicity of NCP. Transepithelial transport (Caco-2) indicated good permeability, with P-app (12.6+/-0.3) x10(-5) cm/s. Importantly, the drug induced glutathione depletion in treated cells and affected the activity of several GSH-dependent enzymes. Conclusion: The novel nucleoside analog

Czech name

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Czech description

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Type

J_x - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

CEP classification

FD - Oncology and haematology

OECD FORD branch

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Project

<a href="/en/project/GAP303%2F11%2F1297" target="_blank" >GAP303/11/1297: Mechanisms of antiviral and cytostatic effects of novel carbocyclic nucleoside analogs</a><br>

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2013

Confidentiality

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

Name of the periodical

Anticancer Research

ISSN

0250-7005

e-ISSN

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Volume of the periodical

33

Issue of the periodical within the volume

8

Country of publishing house

GR - GREECE

Number of pages

6

Pages from-to

3163-3168

UT code for WoS article

000322559300025

EID of the result in the Scopus database

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