Jump to main content
Jump to site search
Access to RSC content Close the message box

Continue to access RSC content when you are not at your institution. Follow our step-by-step guide.

Issue 21, 2017
Previous Article Next Article

Exploitation of new structurally diverse d-glucuronamide-containing N-glycosyl compounds: synthesis and anticancer potential

Author affiliations


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 TMSN3 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 N9-linked purine nucleoside in the breast cancer cell MCF-7 with a GI50 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.

Graphical abstract: Exploitation of new structurally diverse d-glucuronamide-containing N-glycosyl compounds: synthesis and anticancer potential

Back to tab navigation

Supplementary files

Article information

24 Feb 2017
08 May 2017
First published
08 May 2017

Org. Biomol. Chem., 2017,15, 4667-4680
Article type

Exploitation of new structurally diverse D-glucuronamide-containing N-glycosyl compounds: synthesis and anticancer potential

N. M. Xavier, A. Porcheron, D. Batista, R. Jorda, E. Řezníčková, V. Kryštof and M. C. Oliveira, Org. Biomol. Chem., 2017, 15, 4667
DOI: 10.1039/C7OB00472A

Social activity

Search articles by author