title: Synthesis and biological evaluation of 3'-C-ethynyl and 3'-C-(1,4-disubstituted-1,2,3-triazolo) double-headed pyranonucleosides.
abstract: A novel series of 3'-C-ethynyl and 3'-C-(1,4-disubstituted-1,2,3-triazolo) double-headed pyranonucleosides has been designed and synthesized. Reaction of 3-keto glucoside 1 with ethynyl magnesium bromide gave the desired precursor 3-C-ethynyl-1,2:5,6-di-O-isopropylidene-α-D-allofuranose (2). Hydrolysis followed by acetylation led to the 1,2,4,6-tetra-O-acetyl-3-C-ethynyl-β-D-allopyranose (3). Compound 3 was condensed with silylated 5-fluorouracil, uracil, thymine, N4-benzoylcytosine and N6-benzoyladenine, respectively and deacetylated to afford the target 1-(3'-C-ethynyl-β-D-allopyranosyl)nucleosides 5a-c,f,g. Copper-Catalyzed Azide-Alkyne Cycloaddition (CuAAC) reaction was utilized to couple the 3'-C-ethynyl pyranonucleoside derivatives with azidoethyl adenine, 5-fluorouracil and thymine, respectively to afford novel triazole double-headed nucleoside analogs 8a-h. 3'-C-Ethynyl pyranonucleosides and the new double-headed analogues were evaluated for their antiviral and cytostatic activities. Although none of the compounds showed pronounced cytostatic activity and were devoid of a significant antiviral potential, the double-headed nucleoside derivatives 8a, 8c and 8e showed a moderate cytostatic activity against human cervix carcinoma HeLa cells which may be the basis for the synthesis of analogous derivatives with improved cytostatic potential.
authors.affiliation: University of Thessaly, Department of Biochemistry & Biotechnology, Laboratory of Bio-organic Chemistry, 26 Ploutonos Str., 41221 Larissa, Greece.
authors.forename: Christos
authors.initials: C
authors.lastname: Kiritsis
authors.forename: Stella
authors.initials: S
authors.lastname: Manta
authors.forename: Ioannis
authors.initials: I
authors.lastname: Papasotiriou
authors.forename: Evdoxia
authors.initials: E
authors.lastname: Coutouli-Argyropoulou
authors.forename: Sakellarios
authors.initials: S
authors.lastname: Trakossas
authors.forename: Jan
authors.initials: J
authors.lastname: Balzarini
authors.forename: Dimitri
authors.initials: D
authors.lastname: Komiotis
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009705:Nucleosides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D011714:Pyrans / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014780:Viruses / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D009705:Nucleosides; D011714:Pyrans; D014230:Triazoles