Investigational New Drugs

, Volume 2, Issue 1, pp 35–47

Antitumor cell and antimetabolic effects of 5-ethyl-2′-deoxyuridine and 5′-substituted 5-ethyl-2′-deoxyuridine derivatives

  • Jan Balzarini
  • Erik De Clercq
  • Gebhard Kiefer
  • Klaus Keppeler
  • Alfred Buchele
Preclinical Studies

Summary

A series of forty 5′-ester derivatives of 5-ethyl-2′-deoxyuridine (EDU) have been evaluated for their inhibitory effects on the growth and metabolism of murine leukemia L1210 cells. Several EDU esters proved as potent as EDU in their inhibitory effects on L1210 cell growth (inhibitory dose-50: 5–10 μg/ml), suggesting that these esters were readily hydrolyzed to release the parent compound EDU. That the EDU esters had to be hydrolyzed first to EDU was further suggested by the dependence of their antiproliferative action on the thymidine kinase activity of the cells. It was further ascertained that EDU and its esters acquired their antiproliferative effects by an interaction with dCTP biosynthesis, possibly at the CDP ribonucleotide reductase step. Under conditions where thymidine was readily incorporated, we were unable to demonstrate any incorporation of EDU into L1210 cell DNA.

Key words

5-ethyl-2′-deoxyuridine murine leukemia L1210 DNA synthesis 

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Copyright information

© Martinus Nijhoff Publishers 1984

Authors and Affiliations

  • Jan Balzarini
    • 1
  • Erik De Clercq
    • 1
  • Gebhard Kiefer
    • 2
  • Klaus Keppeler
    • 2
  • Alfred Buchele
    • 2
  1. 1.Rega Institute for Medical ResearchKatholieke Universiteit LeuvenLeuvenBelgium
  2. 2.Robugen PharmaceuticalsEsslingenWest Germany
  3. 3.Rega Institute for Medical ResearchKatholieke Universiteit LeuvenLeuvenBelgium

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