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Keywords:

Animals, Antineoplastic Agents, Antiviral Agents, Cell Line, Cercopithecus aethiops, Chemistry, Dideoxynucleosides, Humans, Hydrocarbons, Fluorinated, Leukemia L1210, Microbial Sensitivity Tests, Rabbits, Structure-Activity Relationship, Tumor Cells, Cultured, Science & Technology, Life Sciences & Biomedicine, Chemistry, Medicinal, Pharmacology & Pharmacy, HUMAN IMMUNODEFICIENCY VIRUS, ANTI-HIV ACTIVITY, S-ADENOSYLHOMOCYSTEINE HYDROLASE, REVERSE-TRANSCRIPTASE, 2',3'-DIDEOXYNUCLEOSIDE ANALOGS, DNA-POLYMERASES, NUCLEOSIDE 5'-TRIPHOSPHATES, DERIVATIVES, POTENT, AGENTS, Chemical Phenomena, Chlorocebus aethiops, 0304 Medicinal and Biomolecular Chemistry, 0305 Organic Chemistry, 1115 Pharmacology and Pharmaceutical Sciences, Medicinal & Biomolecular Chemistry, 3214 Pharmacology and pharmaceutical sciences, 3404 Medicinal and biomolecular chemistry, 3405 Organic chemistry

Abstract:

A series of 3'-deoxy-3'-fluoro- and 2'-azido-2',3'-dideoxy-3'-fluoro-D-ribofuranosides of natural heterocyclic bases have been synthesized with the use of universal carbohydrate precursors, viz., 1-O-acetyl-2,5-di-O-benzoyl-3-deoxy-3-fluoro-D-ribofuranose and methyl 2-azido-5-O-benzoyl-2,3-dideoxy-3-fluoro-beta-D-ribofuranoside, respectively. The cytostatic and antiviral activity of the compounds was evaluated against a variety of tumor cell lines and DNA/RNA viruses, respectively. As the most active compound, from both a cytostatic and antiviral activity viewpoint, emerged 3'-deoxy-3'-fluoroadenosine. It inhibited the proliferation of some tumor cell lines (i.e. murine leukemia L1210 and human T-lymphocyte MT-4) at a concentration of 0.2-2 micrograms/mL, and proved inhibitory to the replication of positive-stranded RNA viruses (i.e. polio, Coxsackie, Sindbis, Semliki forest), double-stranded RNA viruses (i.e. reo), and some DNA viruses (i.e. vaccinia) at a concentration of 1-4 micrograms/mL, which is well below the cytotoxicity threshold (40 micrograms/mL).