Inhibition of enzymes of polyamine back-conversion by pentamidine and berenil.
Pentamidine and berenil, clinical antiparasitic amidines, have been found to be potent competitive inhibitors of human spermidine/spermine acetyltransferase (SSAT). Ki values were found to be 2.4 and 2 microM, respectively, with spermidine as substrate. A second enzyme of polyamine back-conversion, murine polyamine oxidase (PAO), was found to be competitively inhibited by pentamidine, with a Ki of 7.6 microM when N-acetylspermine was the substrate. Berenil, on the other hand, was an extremely weak inhibitor (Ki = 120 microM). The implication of the effect of inhibition of polyamine back-conversion on the growth of mammalian parasites is discussed.
Libby
P R
PR
Grace Cancer Drug Center, Roswell Park Cancer Institute, Buffalo, NY 14263.
Porter
C W
CW
D000123:Acetyltransferases / Q000037:antagonists & inhibitors*; D000818:Animals; D004133:Diminazene / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D007939:Leukemia L1210 / Q000201:enzymology; D008545:Melanoma / Q000201:enzymology; D051379:Mice; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000037:antagonists & inhibitors*; D010419:Pentamidine / Q000494:pharmacology*; D000097667:Polyamine Oxidase; D000099228:Diamine N-Acetyltransferase
D000123:Acetyltransferases; D004133:Diminazene; D000587:Oxidoreductases Acting on CH-NH Group Donors; D010419:Pentamidine; D000097667:Polyamine Oxidase; D000099228:Diamine N-Acetyltransferase; C003915:diminazene aceturate