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.
In Vitro Optimization of Non-Small Cell Lung Cancer Activity with Troxacitabine,l-1,3-Dioxolane-cytidine, Prodrugs / Marco Radi;Auke D. Adema;Jonathan R. Daft;Jong H. Cho;Eveline K. Hoebe;Lou-Ella M. M. Alexander;Godefridus J. Peters;Chung K. Chu. - In: JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0022-2623. - 50(2007), pp. 2249-2253. [10.1021/jm0612923]