Exploitation of new structurally diverse d-glucuronamide-containing: Nglycosyl compounds: Synthesis and anticancer potential

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61389030%3A_____%2F17%3A00476598" target="_blank" >RIV/61389030:_____/17:00476598 - isvavai.cz</a>

Alternative codes found

RIV/61989592:15310/17:73584817

Result on the web

<a href="http://dx.doi.org/10.1039/c7ob00472a" target="_blank" >http://dx.doi.org/10.1039/c7ob00472a</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1039/c7ob00472a" target="_blank" >10.1039/c7ob00472a</a>

Result language

angličtina

Original language name

Exploitation of new structurally diverse d-glucuronamide-containing: Nglycosyl compounds: Synthesis and anticancer potential

Original language description

The synthesis and anticancer evaluation of novel N-glycosyl derivatives containing N-substituted glucuronamide moieties, as nucleoside analogs or as prospective mimetics of glycosyl phosphates or of nucleotides, is reported. These compounds comprise N-anomerically-linked nucleobases or motifs that are surrogates of a phosphate group, such as sulfonamide or phosphoramidate moieties. 1-Sulfonamido glucuronamides containing N-benzyl, N-propargyl or N-dodecyl carboxamide units were synthesized through glycosylation of methanesulfonamide with tetra-O-acetyl glucuronamides. 1-Azido glucuronamides were accessed by microwave-assisted reactions of tetra-O-acetyl glucuronamides with TMSN 3 and were further converted into N-glycosylphosphoramidates by treatment with trimethyl phosphite. Potential glucuronamide-based nucleotide mimetics comprising both an anomeric sulfonamide/phosphoramidate group and a benzyltriazolylmethyl amide system at C-5, as nucleobase mimetics, were synthesized via 'click' cycloaddition of N-propargyl glucuronamide derivatives with benzyl azide. N-Dodecyl tetra-O-acetyl glucuronamides were converted into uracil and purine nucleosides via N-glycosylation of the corresponding silylated nucleobases. Biological screening revealed significant antiproliferative activities of the N-dodecyl glucuronamide-containing sulfonamide, phosphoramidate and nucleosides in K562 and MCF-7 cells. The highest effect was exhibited by the N 9linked purine nucleoside in the breast cancer cell MCF-7 with a GI 50 value similar to that of clinically used 5-fluorouracil. Immunoblotting and cell cycle analysis of K562 cells treated with the most active compound as well as evaluation of the effect of this nucleoside on the activities of caspases 3 and 7 showed induction of apoptosis as the mechanism of cell death.

Czech name

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Czech description

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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

Organic & Biomolecular Chemistry

ISSN

1477-0520

e-ISSN

—

Volume of the periodical

15

Issue of the periodical within the volume

21

Country of publishing house

GB - UNITED KINGDOM

Number of pages

14

Pages from-to

4667-4680

UT code for WoS article

000402742300023

EID of the result in the Scopus database

2-s2.0-85021761785