In vitro optimization of non-small cell lung cancer activity with troxacitabine, L-1,3-dioxolane-cytidine, prodrugs |
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Authors: | Radi Marco Adema Auke D Daft Jonathan R Cho Jong H Hoebe Eveline K Alexander Lou-Ella M M Peters Godefridus J Chu Chung K |
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Affiliation: | The University of Georgia College of Pharmacy, Athens, Georgia 30602, USA. |
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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. |
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