Cationic porphyrin derivatives as inhibitors of polyamine catabolism.
The effects of six cationic porphyrins on several enzymes involved in polyamine biosynthesis and catabolism have been examined. Both spermidine and spermine synthase were unaffected by the porphyrins at up to 2 mM. By contrast, ornithine and S-adenosylmethionine decarboxylase were inhibited by the nickel and cobalt derivatives of meso-tetrakis(N-methyl-4-pyridiniumyl)porphyrin (T4MPyP) with IC50 values in the 10-100 microM region. Spermidine/spermine N1-acetyltransferase (SSAT) and polyamine oxidase (PAO) were highly sensitive to the six meso-substituted cationic porphyrins tested, with Ki values as low as 6 nM for SSAT and 85 nM for PAO. These inhibitors may prove useful in defining the structural features of the active site of these enzymes.
Libby
P R
PR
Department of Experimental Therapeutics, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
Munson
B R
BR
Fiel
R J
RJ
Porter
C W
CW
D000123:Acetyltransferases / Q000037:antagonists & inhibitors; D012437:Adenosylmethionine Decarboxylase / Q000037:antagonists & inhibitors; D000818:Animals; D015317:Biogenic Polyamines / Q000096:biosynthesis / Q000378:metabolism*; D002384:Catalysis; D002412:Cations; D002614:Chelating Agents / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D007939:Leukemia L1210 / Q000201:enzymology; D008545:Melanoma / Q000201:enzymology; D065108:Ornithine Decarboxylase Inhibitors; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000037:antagonists & inhibitors; D011166:Porphyrins / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D000097667:Polyamine Oxidase; D000099228:Diamine N-Acetyltransferase
D000123:Acetyltransferases; D012437:Adenosylmethionine Decarboxylase; D015317:Biogenic Polyamines; D002412:Cations; D002614:Chelating Agents; D004791:Enzyme Inhibitors; D065108:Ornithine Decarboxylase Inhibitors; D000587:Oxidoreductases Acting on CH-NH Group Donors; D011166:Porphyrins; D000097667:Polyamine Oxidase; D000099228:Diamine N-Acetyltransferase; C092399:meso-tetrakis(1-methyl-4-pyridiniumyl)porphyrin