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

  • J Med Chem. 2007 May 3;50(9):2249-53. doi: 10.1021/jm0612923.
Marco Radi  1 ,  Auke D Adema ,  Jonathan R Daft ,  Jong H Cho ,  Eveline K Hoebe ,  Lou-Ella M M Alexander ,  Godefridus J Peters ,  Chung K Chu
Affiliations
  • 1. The University of Georgia College of Pharmacy, Athens, Georgia 30602, USA.
PMID: 17419604 DOI: 10.1021/jm0612923
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.