| abstract |
The main drawback in the use of most nucleoside anticancer agents originates from their hydrophilic nature, of which property requires a high and frequent dosage for an intravenous administration. Unlike other nucleoside anti-tumor agents, troxacitabine appears to predominantly enter tumor cells by passive diffusion rather then by using nucleoside transporters, although this may be model dependent. Accordingly, in the present work, a small library of twenty troxacitabine prodrugs has been synthesized using a parallel approach in order to evaluate the relationship between the lipophilicity of the prodrugs and their antitumor activity. Biological evaluation of the prodrugs on two non-small cell lung cancer cell lines (A549 and SW1573) and in pancreatic cell lines clearly showed better antitumor activity than that of troxacitabine, with IC 50 values in the nanomolar range. |