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  • Title: Antitumor activity of alkylesters of 5-fluoro-2'-deoxyuridine 5'-monophosphate (FdUMP) against murine lymphoma L5178Y resistant to 5-fluoro-2'-deoxyuridine.
    Author: Kanzawa F, Matsushima Y, Ishihara J, Hoshi A, Ohba T, Watanabe K.
    Journal: J Pharmacobiodyn; 1986 Aug; 9(8):688-93. PubMed ID: 2946859.
    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'-deoxyuridine). 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 on the C-3' position. Eicosyl-FdUMP was found to show no or low cross-resistance on the L5178Y/FUdR subline which was about 19 000-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.
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