Journal of Pharmacobio-Dynamics
Online ISSN : 1881-1353
Print ISSN : 0386-846X
ISSN-L : 0386-846X
ANTITUMOR ACTIVITY OF ALKYLESTERS OF 5-FLUORO-2'-DEOXYURIDINE 5'-MONOPHOSPHATE (FDUMP) AGAINST MURINE LYMPHOMA L5178Y RESISTANT TO 5-FLUORO-2'-DEOXYURIDINE
FUMIHIKO KANZAWAYUKA MATSUSHIMAJUNICHI ISHIHARAAKIO HOSHITAKEO OHBAKENZO WATANABE
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キーワード: cross resistance
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1986 年 9 巻 8 号 p. 688-693

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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.

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© The Pharmaceutical Society of Japan
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