Novel Fluorinated Antifolates. Enzyme Inhibition and Cytotoxicity Studies on 2′- and 3′-Fluoroaminopterin

Jack Henkin, Wendy L. Washtien

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Two novel analogues of aminopterin with a single fluorine substitution in the 21 (compound 8) or in the 3’ (compound 9) position of the p-aminobenzoyl group were synthesized and evaluated as inhibitors of dihydrofolate reductase from two bacterial species and from human HeLa cells. The 2′-fluoro compound was bound essentially the same as aminopterin itself, while the 3′-fluoro derivative bound two- to threefold more tightly in all cases. UV spectral shifts indicated normal binding of the pteridine. Cytotoxicity studies against mouse leukemia L1210 cells and the human stomach cancer line HuTu80 indicated equivalent toxicity of the parent drug with the 2′-fluoro analogue. 3′-Fluoroaminopterin was, however, twice as toxic as aminopterin to both cell lines.

Original languageEnglish (US)
Pages (from-to)1193-1196
Number of pages4
JournalJournal of Medicinal Chemistry
Volume26
Issue number8
DOIs
StatePublished - Jan 1 1983

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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