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Synthesis and Biological Evaluation of 3΄-C-Ethynyl and 3΄-C-(1,4-disubstituted-1,2,3-triazolo) Double-Headed Pyranonucleosides.
MedLine Citation:
PMID:  22530902     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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:
Christos Kiritsis; Stella Manta; Ioannis Papasotiriou; Evdoxia Coutouli-Argyropoulou; Sakellarios Trakossas; Jan Balzarini; Dimitri Komiotis
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-4-24
Journal Detail:
Title:  Medicinal chemistry (Shariqah (United Arab Emirates))     Volume:  -     ISSN:  1875-6638     ISO Abbreviation:  -     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-4-25     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101240303     Medline TA:  Med Chem     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Biochemistry and Biotechnology, Laboratory of Bio-organic Chemistry, University of Thessaly, 41221 Larissa, Greece. dkom@bio.uth.gr.
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