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Synthesis and antiproliferative evaluation of novel azido nucleosides and their phosphoramidate derivatives
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SYSNO ASEP 0479189 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Synthesis and antiproliferative evaluation of novel azido nucleosides and their phosphoramidate derivatives Author(s) Xavier, N.M. (PT)
Goncalves-Pereira, R. (PT)
Jorda, Radek (UEB-Q) ORCID, RID
Řezníčková, Eva (UEB-Q) RID, ORCID
Kryštof, Vladimír (UEB-Q) RID, ORCID
Oliveira, M.C. (PT)Number of authors 6 Source Title Pure and Applied Chemistry. - : Walter de Gruyter - ISSN 0033-4545
Roč. 89, č. 9 (2017), s. 1267-1281Number of pages 16 s. Language eng - English Country US - United States Keywords anticancer activity ; azido nucleosides ; bioactive molecules ; ics-28 ; N-glycosylation ; nucleoside phosphoramidates ; nucleoside/nucleotide analogs ; Staudinger-phosphite reaction Subject RIV EB - Genetics ; Molecular Biology OECD category Organic chemistry R&D Projects LO1204 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Institutional support UEB-Q - RVO:61389030 UT WOS 000411393900003 EID SCOPUS 85028515752 DOI 10.1515/pac-2016-1218 Annotation 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. Workplace Institute of Experimental Botany Contact David Klier, knihovna@ueb.cas.cz, Tel.: 220 390 469 Year of Publishing 2018
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