Novel fluorinated antifolates. Enzyme inhibition and cytotoxicity studies on 2'- and 3'-fluoroaminopterin.

Article Details

Citation

Henkin J, Washtien WL

Novel fluorinated antifolates. Enzyme inhibition and cytotoxicity studies on 2'- and 3'-fluoroaminopterin.

J Med Chem. 1983 Aug;26(8):1193-6.

PubMed ID
6410066 [ View in PubMed
]
Abstract

Two novel analogues of aminopterin with a single fluorine substitution in the 2' (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.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
AminopterinDihydrofolate reductaseIC 50 (nM)11N/AN/ADetails
AminopterinDihydrofolate reductaseIC 50 (nM)5N/AN/ADetails
AminopterinDihydrofolate reductaseIC 50 (nM)31N/AN/ADetails