Metabolism of pyrimidine analogues and their nucleosides

George C. Daher, Barry E. Harris, Robert B. Diasio

Research output: Contribution to journalReview articlepeer-review

108 Scopus citations


The pyrimidine antimetabolite drugs consist of base and nucleoside analogues of the naturally occurring pyrimidines uracil, thymine and cytosine. As is typical of antimetabolites, these drugs have a strong structural similarity to endogenous nucleic acid precursors. The structural differences are usually substitutions at one of the carbons in the pyrimidine ring itself or substitutions at one of the hydrogens attached to the ring of the pyrimidine or sugar (ribose or deoxyribose). Despite the differences noted above, these analogues, can still be taken up into cells and then metabolized via anabolic or catabolic pathways used by endogenous pyrimidines. Cytotoxicity results when the antimetabolite either is incorporated in place of the naturally pyrimidine metabolite into a key molecule (such as RNA or DNA) or competes with the naturally occurring pyrimidine metabolite for a critical enzyme. There are four pyrimidine antimetabolites that are currently used extensively in clinical oncology. These include the fluoropyrimidines, fluorouracil and fluorodeoxyuridine, and the cytosine analogues, cytosine arabinoside and azacytidine.

Original languageEnglish (US)
Pages (from-to)189-222
Number of pages34
JournalPharmacology and Therapeutics
Issue number2
StatePublished - 1990

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)


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