Transport mechanisms of a novel antileukemic and antiviral compound 9-norbornyl-6-chloropurine

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F15%3A00443259" target="_blank" >RIV/61388963:_____/15:00443259 - isvavai.cz</a>

Výsledek na webu

<a href="http://dx.doi.org/10.3109/14756366.2013.879576" target="_blank" >http://dx.doi.org/10.3109/14756366.2013.879576</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3109/14756366.2013.879576" target="_blank" >10.3109/14756366.2013.879576</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Transport mechanisms of a novel antileukemic and antiviral compound 9-norbornyl-6-chloropurine

Popis výsledku v původním jazyce

6-Chloropurines substituted at the position 9 with variously modified bicyclic skeletons represent promising antiviral and anticancer agents. This work aimed to investigate the transport mechanisms of 9-[(1R*,2R*,4S*)-bicyclo[2.2.1]hept-2-yl]-6-chloro-9H-purine (9-norbornyl-6-chloropurine, NCP) and their relationship to the metabolism and biological activity of the compound. Transport experiments were conducted in CCRF-CEM cells using radiolabeled compound ([H-3]NCP). The pattern of the intracellular uptake of [H-3]NCP in CCRF-CEM cells pointed to a combination of passive and facilitated diffusion as prevailing transport mechanisms. NCP intracellular metabolism was found to enhance its uptake by modifying NCP concentration gradient. The transport kinetics reached steady state under the conditions of MRP and MDR proteins blockade, indicating that NCP is a substrate for these efflux pumps. Their inhibition also increased the cytotoxicity of NCP. Our findings suggest that the novel nucleo

Název v anglickém jazyce

Transport mechanisms of a novel antileukemic and antiviral compound 9-norbornyl-6-chloropurine

Popis výsledku anglicky

6-Chloropurines substituted at the position 9 with variously modified bicyclic skeletons represent promising antiviral and anticancer agents. This work aimed to investigate the transport mechanisms of 9-[(1R*,2R*,4S*)-bicyclo[2.2.1]hept-2-yl]-6-chloro-9H-purine (9-norbornyl-6-chloropurine, NCP) and their relationship to the metabolism and biological activity of the compound. Transport experiments were conducted in CCRF-CEM cells using radiolabeled compound ([H-3]NCP). The pattern of the intracellular uptake of [H-3]NCP in CCRF-CEM cells pointed to a combination of passive and facilitated diffusion as prevailing transport mechanisms. NCP intracellular metabolism was found to enhance its uptake by modifying NCP concentration gradient. The transport kinetics reached steady state under the conditions of MRP and MDR proteins blockade, indicating that NCP is a substrate for these efflux pumps. Their inhibition also increased the cytotoxicity of NCP. Our findings suggest that the novel nucleo

Druh

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

CEP obor

CE - Biochemie

OECD FORD obor

—

Projekt

<a href="/cs/project/GAP303%2F11%2F1297" target="_blank" >GAP303/11/1297: Mechanismus protivirové a cytostatické aktivity nových karbocyklických analogů nukleosidů</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2015

Kód důvěrnosti údajů

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

Název periodika

Journal of Enzyme Inhibition and Medicinal Chemistry

ISSN

1475-6366

e-ISSN

—

Svazek periodika

30

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

6

Strana od-do

57-62

Kód UT WoS článku

000347956500009

EID výsledku v databázi Scopus

2-s2.0-84921294824