Anticancer conjugates and cocktails based on methotrexate and nucleoside synergism

Anthony R. Vortherms, Hester N. Dang, Robert P. Doyle

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


Conjugates of methotrexate (MTX) and the nucleoside analogs 3-azidodeoxythymidine (AZT), iododeoxyuridine (IUdR) and dideoxycytidine (ddC) linked using poly(ethyleneglycol) are presented. In vitro cytotoxicity assays of the conjugates against drug resistant ovarian cell line A2780/AD are preformed and comparisons made to such assays performed for unconjugated (cocktail) systems. All systems tested were inactive, or had low activity, at 24 h. After 72 hr incubation however, the cocktails of MTX and AZT, IUdR or ddC showed high cytotoxicity in the low nanomolar range. The conjugates were only very moderately active with IC50 values in the [0.1 to 1.0 mM] range. Conjugation of the antifolate to the nucleoside analogs has it seems reduced the activity significantly when compared to a cocktail of the components, indicating a conjugate approach is unlikely to translate into success in vivo. The positive note comes from the observation that by combining two of the new conjugates, namely those based on MTX with IUdR or AZT, an IC50 at 24 hours of ∼ [180 μM] was produced.

Original languageEnglish (US)
Pages (from-to)19-26
Number of pages8
JournalClinical Medicine: Oncology
Issue number3
StatePublished - May 21 2009


  • Cocktail therapy
  • Conjugates
  • Folic acid
  • Nucleosides
  • PEG

ASJC Scopus subject areas

  • Oncology


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