Synthesis and antiproliferative evaluation of novel azido nucleosides and their phosphoramidate derivatives

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61389030%3A_____%2F17%3A00479189" target="_blank" >RIV/61389030:_____/17:00479189 - isvavai.cz</a>

Alternative codes found

RIV/61989592:15310/17:73584818

Result on the web

<a href="http://dx.doi.org/10.1515/pac-2016-1218" target="_blank" >http://dx.doi.org/10.1515/pac-2016-1218</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1515/pac-2016-1218" target="_blank" >10.1515/pac-2016-1218</a>

Result language

angličtina

Original language name

Synthesis and antiproliferative evaluation of novel azido nucleosides and their phosphoramidate derivatives

Original language description

New xylofuranosyl and glucopyranosyl nucleoside phosphoramidates were synthesized as potential mimetics of nucleoside 5′-monophosphates. Their access involved N-glycosylation of uracil and 2-acetamido-6-chloropurine with 5′/6′-azido-1,2-di-O-acetyl glycosyl donors and subsequent Staudinger-phosphite reaction of the resulting azido nucleosides. The coupling of the purine derivative with the pyranosyl donor furnished N 9 A nd N 7linked nucleosides in 1:1 ratio, whereas with the furanosyl donor, the N 9nucleoside was the major regioisomer formed. When using uracil, only 5′/6′-azido N 1linked nucleosides were obtained. The purine 5′/6′-azido nucleosides were converted into corresponding phosphoramidates in good yields. The antiproliferative effects of the nucleoside phosphoramidates and those of the azido counterparts on cancer cells were evaluated. While the nucleoside phosphoramidates did not show significant activities, the purine 5′/6′-azido nucleosides displayed potent effects against K562, MCF-7 and BT474 cell lines. The 5′-azidofuranosyl N 9 and N 7linked purine nucleosides exhibited highest activity towards the chronic myeloid leukemia cell line (K562) with GI 50 values of 13.6 and 9.7 μM, respectively. Among pyranosyl nucleosides, the N 7linked nucleoside was the most active compound with efficacy towards all cell lines assayed and a highest effect on K562 cells (GI 50 =6.8 μM). Cell cycle analysis of K562 and MCF-7 cells showed that the most active compounds cause G2/M arrest.

Czech name

—

Czech description

—

Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10401 - Organic chemistry

Project

<a href="/en/project/LO1204" target="_blank" >LO1204: Sustainable development of research in the Centre of the Region Haná</a><br>

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2017

Confidentiality

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

Name of the periodical

Pure and Applied Chemistry

ISSN

0033-4545

e-ISSN

—

Volume of the periodical

89

Issue of the periodical within the volume

9

Country of publishing house

US - UNITED STATES

Number of pages

16

Pages from-to

1267-1281

UT code for WoS article

000411393900003

EID of the result in the Scopus database

2-s2.0-85028515752