Potential anticancer agents: 5-(N-substituted-aminocarbonyl)- and 5-(N-substituted-aminothiocarbonyl)-5,6,7,8-tetrahydrofolic acids.
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 microM) but noncytotoxic to proliferating L1210 cells. No activity was observed for 7 against the P388 leukemia in mice.
Temple
C
C
Kettering-Meyer Laboratory, Southern Research Institute, Birmingham, Alabama 35255-5305.
Elliott
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RD
Montgomery
J A
JA
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D007939:Leukemia L1210 / Q000188:drug therapy; D007941:Leukemia P388 / Q000188:drug therapy; D051379:Mice; D013763:Tetrahydrofolates / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use
D000970:Antineoplastic Agents; D013763:Tetrahydrofolates; C030371:5,6,7,8-tetrahydrofolic acid