Antitumor activity of alkylesters of 5-fluoro-2'-deoxyuridine 5'-monophosphate (FdUMP) against murine lymphoma L5178Y resistant to 5-fluoro-2'-deoxyuridine.

Publisher Website
Google Scholar
Abstract
A series of twenty six 5''-substituted FdUMP (5-fluoro-2''-deoxyuridine 5''-monophosphate) have been evaluated for their inhibitory effects on the proliferation of murine lymphoma L5178Y cells sensitive or resistant to FUdR (5-fluoro-2''-doexyuridine). 5''-Octylphenylene-FdUMP was the most active among these active derivatives against the parent cell line (L5178Y/P). Several other FdUMP derivatives also proved as potent as FUdR in their antiproliferating activity on the L5178Y/P cell line. Activity of these derivatives was decreased considerably by a substituent with a long aliphatic chain and the introduction of acyl groups of the C-3'' position. Eicosyl-FdUMP was found to show no or low cross-resistance on the L5178Y/FUdR subline which was about 19000-fold resistant to FUdR compared with the parent cell line. This derivative might penetrate cell membrane in an intact form and be converted into FdUMP by a phosphodiesterase inside the cell, because an anabolic enzyme, deoxyuridine kinase, was defective in cells of the L5178Y/FUdR subline. The derivatives were promising as antitumor agents for the treatment of relapsed patients following 5-fluorouracil therapy.