PUTRESCINE UPTAKE INHIBITION BY AROMATIC DIAMIDINES IN LEISHMANIA-INFANTUM PROMASTIGOTES

The effect of a series of aromatic diamidines has been tested on Leish mania infantum promastigotes in both culture growth and putrescine upt ake. The EC(50) values calculated by means of dose-response curves wer e 45, 80, 165, 259 and 600 mu M for 4',6-diamidino-2-phenylindole (DAP I), dibromo propamidine, pentamidine 2-hydroxy stilbamidine and stilba midine, respectively, although no inhibitory effects on cell growth we re found at 1 mM propamidine, phenamidine and amicarbalide. When these compounds were kinetically analysed for putrescine uptake using Linew eaver-Burk plots, the K-i values reached were: DAPI, 15 mu M; pentamid ine, 3 mu M; dibromo propamidine, 7 mu M; 2-hydroxy stilbamidine, 21 m u M; stilbamidine, 20 mu M; propamidine, 25 mu M; and phenamidine, 95 mu M. Amicarbalide, however, was not able to reduce putrescine uptake to a significant extent, even at the highest concentration studied of 1 mM.