Fluoro-ketopyranosyl nucleosides: synthesis and biological evaluation of 3-fluoro-2-keto-beta-D-glucopyranosyl derivatives of N4-benzoyl cytosine.
1,2:5,6-Di-O-isopropylidene-alpha-d-glucofuranose on mild oxidation, reduction, fluorination, and deisopropylidenation followed by acetylation gave peracetylated 3-deoxy-3-fluoro-d-glucopyranose. This was coupled with silylated N(4)-benzoyl cytosine. The nucleoside was deacetylated and after several subsequent protection and deprotection steps afforded the desired 3-fluoro-2-keto-beta-d-glucopyranosyl derivatives. These novel synthesized compounds were evaluated for antiviral and cytotoxic activities against rotavirus, vesicular stomatitis virus, and the human colon adenocarcinoma cell line Caco-2, and have a promising potential in combating the rotaviral infections and in the treatment of colon cancer. As compared to AZT, a nucleoside analogue of reverse transcriptase inhibitor, the novel synthesized 1-(3,4-dideoxy-3-fluoro-beta-d-glycero-hex-3-enopyranosyl-2-ulose)-N(4)-benzoyl cytosine showed to be more effective at lower concentrations in inhibition of rotavirus infection as well as in the same range of antitumor activity.
Manta
Stella
S
Department of Biochemistry and Biotechnology, Laboratory of Organic Chemistry, University of Thessaly, Larissa, Greece.
Agelis
George
G
Botić
Tanja
T
Cencic
Avrelija
A
Komiotis
Dimitri
D
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D018938:Caco-2 Cells; D002417:Cattle; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003596:Cytosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D000882:Haplorhini; D006801:Humans; D007202:Indicators and Reagents; D009005:Monosaccharides / Q000138:chemical synthesis* / Q000494:pharmacology*; D010084:Oxidation-Reduction; D013552:Swine; D014721:Vesicular stomatitis Indiana virus / Q000187:drug effects; D015215:Zidovudine / Q000494:pharmacology
D000970:Antineoplastic Agents; D000998:Antiviral Agents; D007202:Indicators and Reagents; D009005:Monosaccharides; D015215:Zidovudine; D003596:Cytosine