Journal of Medicinal Chemistry p. 697 - 700 (1988)
Update date:2022-08-04
Topics: Molecular docking Cytotoxicity Enzyme inhibition In Vitro Assays Antifolate
Temple Jr.
Elliott
Montgomery
5-[[N-[(Ethoxycarbonyl)alkyl]amino]carbonyl] (6-9) and the corresponding aminothiocarbonyl (12-15) derivatives of 5,6,7,8-tetrahydrofolic acid were prepared as multisubstrate analogues of the substrate-cofactor adduct in the reactions catalyzed by the folate-mediated one-carbon transfer reactions. Evaluation in vitro showed that 7 (alkyl = hexyl) was cytotoxic to H.Ep-2 cells (ED50, 4 μM) but noncytotoxic to proliferating L1210 cells. No activity was observed for 7 against the P388 leukemia in mice.
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