Novel dodecyl-containing azido and glucuronamide-based nucleosides exhibiting anticancer potential
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61389030%3A_____%2F19%3A00507563" target="_blank" >RIV/61389030:_____/19:00507563 - isvavai.cz</a>
Alternative codes found
RIV/61989592:15310/19:73598619
Result on the web
<a href="http://dx.doi.org/10.1515/pac-2019-0106" target="_blank" >http://dx.doi.org/10.1515/pac-2019-0106</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1515/pac-2019-0106" target="_blank" >10.1515/pac-2019-0106</a>
Alternative languages
Result language
angličtina
Original language name
Novel dodecyl-containing azido and glucuronamide-based nucleosides exhibiting anticancer potential
Original language description
The synthesis and anticancer evaluation of new series of nucleosides constructed on 5/6-azidoglycosyl or glucuronamide moieties and containing an O- or an N-dodecyl chain, respectively, are disclosed. Based on our previous results, their structures were planned to preclude them to act via a similar metabolic pathway than that of clinically used nucleoside antimetabolites, against which cancer cells frequently acquire resistance. Xylo and gluco-configured 5/6-azido-1,2-di-O-acetyl furanosyl and pyranosyl donors containing a 3-O-dodecyl group were synthesized from diacetone-d-glucose and were subsequently coupled with silylated uracil or 2-acetamido-6-chloropurine. N-Dodecyl glucuronamide-based nucleosides were accessed from acetonide-protected glucofuranurono-6,3-lactone, which was converted in few steps into O-benzylated 1,2-di-O-acetyl furanuronamide or pyranuronamide derivatives to undergo further N-glycosylation. Both types of nucleosides demonstrated notorious antiproliferative effects in chronic myeloid leukemia (K562) and in breast cancer (MCF-7) cells. The most potent molecules were a 6′-azidoglucopyranosyl N7-linked purine nucleoside and glucofuranuronamide derivatives comprising N1-linked uracil and N7-linked purine units with activities in the single-digit micromolar order of concentration against both cell lines. Their GI50 values in MCF-7 cells were similar or ca. 3-fold lower than that of the standard drug 5-fluorouracil. Cell cycle studies and immunoblotting analysis of apoptosis-associated proteins in treated K562 cells indicated that the antiproliferative effect of the most effective nucleosides is based on apoptosis induction.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30205 - Hematology
Result continuities
Project
<a href="/en/project/EF16_019%2F0000868" target="_blank" >EF16_019/0000868: Molecular, cellular and clinical approach to healthy ageing</a><br>
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2019
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Pure and Applied Chemistry
ISSN
0033-4545
e-ISSN
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Volume of the periodical
91
Issue of the periodical within the volume
7
Country of publishing house
DE - GERMANY
Number of pages
21
Pages from-to
1085-1105
UT code for WoS article
000475296300003
EID of the result in the Scopus database
2-s2.0-85064707260