Abstract
l-1,3-Dioxolane-cytidine, a potent anticancer agent against leukemia, has limited efficacy against solid tumors, perhaps due to its hydrophilicity. Herein, a library of prodrugs were synthesized to optimize in vitro antitumor activity against non-small cell lung cancer. N4-Substituted fatty acid amide prodrugs of 10-16 carbon chain length demonstrated significantly improved antitumor activity over l-1,3-dioxolane-cytidine. These in vitro results suggest that the in vivo therapeutic efficacy of l-1,3-dioxolane-cytidine against solid tumors may be improved with prodrug strategies.
MeSH terms
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Antineoplastic Agents / chemical synthesis*
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / pharmacology
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Carcinoma, Non-Small-Cell Lung / drug therapy*
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Cell Line, Tumor
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Cytosine / analogs & derivatives*
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Cytosine / chemical synthesis
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Cytosine / chemistry
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Cytosine / pharmacology
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Dioxolanes / chemical synthesis*
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Dioxolanes / chemistry
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Dioxolanes / pharmacology
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Drug Screening Assays, Antitumor
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Humans
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Lung Neoplasms / drug therapy*
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Prodrugs / chemical synthesis*
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Prodrugs / chemistry
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Prodrugs / pharmacology
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Stereoisomerism
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Structure-Activity Relationship
Substances
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Antineoplastic Agents
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Dioxolanes
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Prodrugs
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troxacitabine
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Cytosine