Publication Type Journal Article
Title Exploitation of new structurally diverse D-glucuronamide-containing N-glycosyl compounds: synthesis and anticancer potential
Authors Nuno Manuel Xavier Alexandre Porcheron Daniela Batista Radek Jorda Eva Reznickova Vladimir Krystof M. Conceição Oliveira
Groups BioMol HC
Journal ORGANIC & BIOMOLECULAR CHEMISTRY
Year 2017
Month June
Volume 15
Number 21
Pages 4667-4680
Abstract 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 N-9-linked 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.
DOI http://dx.doi.org/10.1039/c7ob00472a
ISBN
Publisher ROYAL SOC CHEMISTRY
Book Title
ISSN 1477-0520
EISSN 1477-0539
Conference Name
Bibtex ID ISI:000402742300023
Observations
Back to Publications List