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). K(i) values were found to be 2.4 and 2-mu-M, 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 K(i) of 7.6-mu-M when N-acetylspermine was the substrate. Berenil, on the other hand, was an extremely weak inhibitor (K(i) = 120-mu-M). The implication of the effect of inhibition of polyamine back-conversion on the growth of mammalian parasites is discussed.