Publication Type Journal Article
Title Synthesis and antiproliferative evaluation of novel azido nucleosides and their phosphoramidate derivatives
Authors Nuno Manuel Xavier Rita Goncalves-Pereira Radek Jorda Eva Reznickova Vladimir Krystof M. Conceição Oliveira
Groups BioMol HC
Journal PURE AND APPLIED CHEMISTRY
Year 2017
Month September
Volume 89
Number 9
Pages 1267-1281
Abstract New xylofuranosyl and glucopyranosyl nucleoside phosphoramidates were synthesized as potential mimetics of nucleoside 5 -monophosphates. Their access involved N-glycosylation of uracil and 2-acet-amido-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- and N-7-linked nucleosides in 1: 1 ratio, whereas with the furanosyl donor, the N-9-nucleoside was the major regioisomer formed. When using uracil, only 5 /6 -azido N-1-linked 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-7-linked purine nucleosides exhibited highest activity towards the chronic myeloid leukemia cell line (K562) with GI(50) values of 13.6 and 9.7 mu M, respectively. Among pyranosyl nucleosides, the N-7-linked nucleoside was the most active compound with efficacy towards all cell lines assayed and a highest effect on K562 cells (GI(50) = 6.8 mu M). Cell cycle analysis of K562 and MCF-7 cells showed that the most active compounds cause G2/M arrest.
DOI http://dx.doi.org/10.1515/pac-2016-1218
ISBN
Publisher
Book Title
ISSN 0033-4545
EISSN 1365-3075
Conference Name
Bibtex ID ISI:000411393900003
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