Biologic activity of a nucleotide conjugate between mitomycin c and cytarabine monophosphate

Robert T. Dorr, D. James

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

A dual prodrug conjugate between the antimetabolite cytarabine monophosphate and the alkylating agent 2,7-diaminomitosene (derived from mitomycin C), cytaramycin, was synthesized and tested for antileukemic activity in sensitive and resistant tumors. The compound was active against parental L-1210, CCRF-CEM, HL-60 and K-562 leukemia cells but did not overcome resistance in sublines developed for (1) multidrug resistance (L-1210/MDR and K-562-R) or (2) for cytarabine resistance (CCRF-CEM/ARA-C and HL-60/ARA-C). Alkaline DNA elution tests demonstrate a predominance of strand breaking activity due to the cytarabine moiety, and a lesser degree of DNA crosslinking, due to the mitosene moiety. The conjugate was active in mice bearing P-388 leukemia (80% increased lifespan), but was not more effective than mitomycin C alone in mice bearing a cytarabine-resistant L-1210 cell line (38% to 31% increased lifespan). These findings suggest that mitomycin nucleotide conjugates do not overcome resistance to the parent antimetabolites.

Original languageEnglish (US)
Pages (from-to)1655-1667
Number of pages13
JournalNucleosides and Nucleotides
Volume13
Issue number8
DOIs
StatePublished - Sep 1 1994

ASJC Scopus subject areas

  • Biochemistry
  • Genetics

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