In vitro optimization of non-small cell lung cancer activity with troxacitabine, L-1,3-dioxolane-cytidine, prodrugs.
Journal of medicinal chemistry 2007 May 3; 50(9):2249-53
Radi M, Adema A AD, Daft J JR, Cho J JH, Hoebe E EK, Alexander L LE, Peters G GJ, Chu C CK
The University of Georgia College of Pharmacy, Athens, Georgia 30602, USA.
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.