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 language||English (US)|
|Number of pages||4|
|Journal||Journal of Medicinal Chemistry|
|State||Published - Aug 1983|
ASJC Scopus subject areas
- Molecular Medicine
- Drug Discovery