Inhibition of ornithine decarboxylase by the isomers of 1,4-dimethylputrescine.
1,4-Dimethylputrescine (2,5-hexanediamine) was separated into its racemic and meso isomers by fractional crystallization of its dibenzoyl derivative. The racemic form was resolved into its (+)- and (-)-isomers with (+)- and (-)-dibenzoyltartaric acids. None of the three isomers (meso, +, and -) inhibited ornithine decarboxylase (ODC) activity in vitro, while all the three were strongly inhibitory of ODC when assayed in vivo in rats or in H-35 hepatoma cells. In rat liver the three isomers also decreased the putrescine pool while only the (+)-isomer decreased spermidine content. In the H-35 cells the (-)- and (+)-isomers decreased the spermidine and spermine content. When ODC was induced in the latter by insulin it was found that the (-)-isomer strongly inhibited protein and ODC synthesis, while the (+)-isomer and the meso isomer were less inhibitory. The meso isomer was a good inducer of ODC antizyme in rat liver, while the (+)- and (-)-isomers were poor inducers of the former.
Moyano
N
N
Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Argentina.
Frydman
J
J
Buldain
G
G
Ruiz
O
O
Frydman
R B
RB
D000818:Animals; D002460:Cell Line; D005260:Female; D007536:Isomerism; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008114:Liver Neoplasms, Experimental; D009363:Neoplasm Proteins / Q000096:biosynthesis; D009904:Optical Rotation; D065108:Ornithine Decarboxylase Inhibitors; D011073:Polyamines / Q000378:metabolism; D011700:Putrescine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000302:isolation & purification / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship; D013853:Thioacetamide / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D009363:Neoplasm Proteins; D065108:Ornithine Decarboxylase Inhibitors; D011073:Polyamines; D013853:Thioacetamide; C057951:1,4-dimethylputrescine; D011700:Putrescine