Abstract
Enantiomers of 4'-aza-2',3'-dideoxynucleosides have been prepared by two different synthetic approaches, on the basis of 1,3-dipolar cycloaddition of a chiral nitrone. Cytotoxicity and apoptotic activity have been investigated. (5'S)-5-Fluoro-1-isoxazolidin-5-yl-1H-pyrimidine-2,4-dione [(-)-AdFU], while showing low level of cytotoxicity, is a good inductor of apoptosis on lymphoid and monocytoid cells, acting as a strong potentiator of Fas-induced cell death.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antineoplastic Agents / chemical synthesis
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Antineoplastic Agents / pharmacology
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Antineoplastic Agents / toxicity
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Antiviral Agents / chemical synthesis
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Antiviral Agents / pharmacology
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Antiviral Agents / toxicity
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Apoptosis
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Caspase 3
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Caspase 8
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Caspase 9
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Caspase Inhibitors
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Caspases / metabolism
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Cell Line
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Dideoxynucleosides / chemical synthesis*
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Dideoxynucleosides / pharmacology
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Dideoxynucleosides / toxicity
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Humans
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Isoxazoles / chemical synthesis*
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Isoxazoles / pharmacology
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Isoxazoles / toxicity
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Lymphoid Tissue / cytology
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Molecular Conformation
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Monocytes / cytology
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Quantum Theory
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Stereoisomerism
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Structure-Activity Relationship
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Tumor Cells, Cultured
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Uridine / analogs & derivatives
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Uridine / chemical synthesis*
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Uridine / pharmacology
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Uridine / toxicity
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fas Receptor / physiology
Substances
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5-fluoro-1-isoxazolidin-5-yl-1H-pyrimidine-2,4-dione
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Antineoplastic Agents
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Antiviral Agents
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Caspase Inhibitors
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Dideoxynucleosides
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Isoxazoles
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fas Receptor
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CASP3 protein, human
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CASP8 protein, human
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CASP9 protein, human
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Caspase 3
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Caspase 8
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Caspase 9
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Caspases
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Uridine