J Med Chem. 2007 May 3;50(9):2249-53. Epub 2007 Apr 10.

In vitro optimization of non-small cell lung cancer activity with troxacitabine, L-1,3-dioxolane-cytidine, prodrugs.

Radi M, Adema AD, Daft JR, Cho JH, Hoebe EK, Alexander LE, Peters GJ, Chu CK.

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The University of Georgia College of Pharmacy, Athens, Georgia 30602, USA.

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.

PMID:: 17419604; [PubMed - indexed for MEDLINE]

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In vitro optimization of non-small cell lung cancer activity with troxacitabine, L-1,3-dioxolane-cytidine, prodrugs.

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