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

Jack Henkin, Wendy L. Washtien

    Research output: Contribution to journalArticlepeer-review

    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 - Aug 1983

    ASJC Scopus subject areas

    • Molecular Medicine
    • Drug Discovery

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