Putrescine uptake inhibition by aromatic diamidines in Leishmania infantum promastigotes

The effect of a series of aromatic diamidines has been tested on Leishmania infantum promastigotes in both culture growth and putrescine uptake. The EC50 values calculated by means of dose-response curves were 45, 80, 165, 259 and 600 microM for 4', 6-diamidino-2-phenylindole (DAPI), dibromo propamidine, pentamidine 2-hydroxy stilbamidine and stilbamidine, respectively, although no inhibitory effects on cell growth were found at 1 mM propamidine, phenamidine and amicarbalide. When these compounds were kinetically analysed for putrescine uptake using Lineweaver-Burk plots, the Ki values reached were: DAPI, 15 microM; pentamidine, 3 microM; dibromo propamidine, 7 microM; 2-hydroxy stilbamidine, 21 microM; stilbamidine, 20 microM; propamidine, 25 microM; and phenamidine, 95 microM. Amicarbalide, however, was not able to reduce putrescine uptake to a significant extent, even at the highest concentration studied of 1 mM.