139895-40-2Relevant academic research and scientific papers
Synthesis and biological activity of novel folic acid analogues: Pteroyl- S-alkylhomocysteine sulfoximines
Harvison,Kalman
, p. 1227 - 1233 (1992)
The synthesis of a novel series of γ-substituted folic acid analogues, pteroyl-S-alkyl-DL-homocysteine (RS)-sulfoximines, and the corresponding S- methylhomocysteine sulfone is described. Side reactions of the sulfoximine groups of the amino acid ester reactants were considered. The correct structures of the isolated target compounds were confirmed by NMR and FAB/MS excluding other alternatives. The replacement of the γ-COOH of the glutamate moiety of folic acid with S-alkylsulfoximine groups of S-methylsulfone did not affect the substrate activity of the vitamin for dihydrofolate reductase. The resulting tetrahydrofolate analogues could serve as cofactors for the thymidylate synthase cycle of murine leukemia L1210 cells in situ. The analogues inhibited the growth of these cells in culture with 2 orders of magnitude lower IC50 values [(2-4) x 10-4 M] than the parent folic acid.
