- 著者
- FUMIHIKO KANZAWA YUKA MATSUSHIMA JUNICHI ISHIHARA AKIO HOSHI TAKEO OHBA KENZO WATANABE
- 出版者
- The Pharmaceutical Society of Japan
- 雑誌
- Journal of Pharmacobio-Dynamics (ISSN:0386846X)
- 巻号頁・発行日
- vol.9, no.8, pp.688-693, 1986 (Released:2008-02-19)
- 参考文献数
- 16
- 被引用文献数
- 5 5
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 decresed 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 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.