Abstract
Background:
4'-seleno-homonucleosides were synthesized as next-generation nucleosides, and their cellular phosphorylation was studied to confirm the hypothesis that bulky selenium atom can sterically hinder the approach of cellular nucleoside kinase to the 5'-OH for phosphorylation.
Results:
4'-seleno-homonucleosides (n = 2), with one-carbon homologation, were synthesized through a tandem seleno-Michael addition-SN2 ring cyclization. LC-MS analysis demonstrated that they were phosphorylated by cellular nucleoside kinases, resulting in anticancer activity.
Conclusion:
The bulky selenium atom played a key role in deciding the phosphorylation by cellular nucleoside kinases. [Formula: see text].
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antineoplastic Agents / chemical synthesis*
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / metabolism*
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Antineoplastic Agents / pharmacology
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Cell Line, Tumor
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Drug Design
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Humans
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Neoplasms / drug therapy
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Neoplasms / metabolism
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Nucleosides / chemical synthesis*
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Nucleosides / chemistry
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Nucleosides / metabolism*
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Nucleosides / pharmacology
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Organoselenium Compounds / chemical synthesis*
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Organoselenium Compounds / chemistry
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Organoselenium Compounds / metabolism*
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Organoselenium Compounds / pharmacology
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Phosphorylation
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Phosphotransferases / metabolism*
Substances
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Antineoplastic Agents
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Nucleosides
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Organoselenium Compounds
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Phosphotransferases
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nucleoside phosphotransferase