Difluoro-phenyl-ethyl(4-aminopropylamidinohydrazone): an irreversible inhibitor for both ornithine and S-adenosylmethionine decarboxylases and its effect on human lymphoid leukemia Molt 4B cells.
Difluoro-phenyl-ethyl(4-aminopropylamidinohydrazone) (DFPA) was synthesized as an irreversible inhibitor of ornithine and S-adenosylmethionine decarboxylases and analyzed for antiproliferative effects on leukemia cells. The compound irreversibly inhibited ornithine and S-adenosylmethione decarboxylases. This inhibition could not be reversed by dialysis or chromatography on Sephadex G-50. When human lymphoid leukemia Molt 4B cells were cultured in the presence of the inhibitor, the intracellular levels of polyamines (putrescine, spermidine and spermine) and the rate of cell proliferation were markedly depressed. In these polyamine-depleted and growth-retarded cells, the synthesis of protein, but not of DNA or RNA, was observed to be significantly inhibited.
Hibasami
H
H
Department of Biochemistry, Mie University School of Medicine, Japan.
Sakurai
M
M
Maekawa
S
S
Murata
T
T
Nakashima
K
K
D012437:Adenosylmethionine Decarboxylase / Q000037:antagonists & inhibitors*; D002262:Carboxy-Lyases / Q000037:antagonists & inhibitors*; D002455:Cell Division / Q000187:drug effects; D003959:Diamines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006835:Hydrazones / Q000494:pharmacology*; D007945:Leukemia, Lymphoid / Q000473:pathology*; D065108:Ornithine Decarboxylase Inhibitors; D014407:Tumor Cells, Cultured / Q000187:drug effects
D003959:Diamines; D006835:Hydrazones; D065108:Ornithine Decarboxylase Inhibitors; C055717:phenyl-(2-difluoroethyl)-4-aminopropylamidinohydrazone; D002262:Carboxy-Lyases; D012437:Adenosylmethionine Decarboxylase