Inhibition of mammalian spermine synthase by N-alkylated-1,3-diaminopropane derivatives in vitro and in cultured rat hepatoma cells.
A number of N-alkylated-1,3-diaminopropane derivatives [H2N-(CH2)3-NH-(CH2)nH, where n = 1-9] have been tested as potential inhibitors of partially purified rat hepatoma (HTC) cell or pure bovine spleen spermine synthase. Among the compounds described in this paper, the most potent competitive inhibitor of spermine synthase, with respect to spermidine, is N-butyl-1,3-diaminopropane with Ki values of 11.9 nM and 10.4 nM for the HTC cell and bovine spleen enzymes respectively. Inhibition of spermine synthase by this alkylated amine is selective since spermidine synthase activity is not affected up to 100 microM N-butyl-1,3-diaminopropane at a range of 5-200 microM putrescine. Added to the culture medium of growing HTC cells, N-butyl-1,3-diaminopropane causes the expected changes in the polyamine levels with a marked decrease of spermine and an increase of spermidine. Under these conditions cell growth continues unabated. Such N-alkylated-1,3-diaminopropane derivatives may have considerable potential as tools for studying the role of polyamines and in particular the functions of spermine in cell multiplication and differentiation.
Baillon
J G
JG
Merrell Dow Research Institute, Strasbourg, France.
Kolb
M
M
Mamont
P S
PS
D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D003959:Diamines / Q000494:pharmacology*; D008114:Liver Neoplasms, Experimental / Q000201:enzymology* / Q000473:pathology; D011700:Putrescine / Q000032:analysis; D051381:Rats; D013095:Spermidine / Q000032:analysis; D011436:Spermidine Synthase / Q000037:antagonists & inhibitors; D013096:Spermine / Q000032:analysis; D013097:Spermine Synthase / Q000037:antagonists & inhibitors*; D013154:Spleen / Q000187:drug effects / Q000201:enzymology*; D014166:Transferases / Q000037:antagonists & inhibitors*
D003959:Diamines; D013096:Spermine; C058695:N-butyl-1,3-diaminopropane; D014166:Transferases; D011436:Spermidine Synthase; D013097:Spermine Synthase; D013095:Spermidine; D011700:Putrescine