Abstract
1-O-Acetyl-2-deoxy-3,5-di-O-toluoyl-4-thio-D-erythro-pentofuranose and 2-deoxy-1,3,5-tri-O-acetyl-4-thio-L-threo-pentofuranose were coupled with 5-azacytosine to obtain alpha and beta anomers of nucleosides. All four nucleosides were reduced to the corresponding dihydro derivatives and deblocked to give target compounds. All eight target compounds were evaluated in a series of human cancer cell lines in culture. Only 2'-deoxy-4'-thio-5-azacytidine (3beta) was found to be cytotoxic in all the cell lines and was further evaluated in vivo. Details of the synthesis and biological activity are reported.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Antineoplastic Agents / chemical synthesis
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Antineoplastic Agents / pharmacology
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Azacitidine / analogs & derivatives*
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Azacitidine / chemical synthesis
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Azacitidine / pharmacology
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Carbohydrate Conformation
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Cell Line, Tumor
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Cell Survival / drug effects
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Cytidine / analogs & derivatives
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Cytosine / analogs & derivatives*
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Cytosine / chemistry
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Drug Screening Assays, Antitumor
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Humans
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Magnetic Resonance Spectroscopy
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Molecular Structure
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Pentoses / chemistry
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Pyrimidine Nucleosides / chemical synthesis
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Pyrimidine Nucleosides / pharmacology
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Sulfur Compounds / chemistry
Substances
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4-thio-2-deoxy-pentofuranose
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Antineoplastic Agents
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Pentoses
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Pyrimidine Nucleosides
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Sulfur Compounds
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5-azacytosine
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Cytidine
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Cytosine
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Azacitidine