Putrescine uptake inhibition by aromatic diamidines in leishmania infantum promastigotes

Abstract

The effect of a series of aromatic diamidines has been tested on Leishmania infantum promastigotes in both culture growth and putrescine uptake. The EC 50 values calculated by means of dose-response curves were 45, 80, 165, 259 and 600 μm 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 K i , values reached were: DAPI, 15 μM; pentamidine, 3 μm; dibromo propamidine, 7 μM; 2-hydroxy stilbamidine, 21 μM; stilbamidine, 20 μM; propamidine, 25 μm; and phenamidine, 95 μM. Amicarbalide, however, was not able to reduce putrescine uptake to a significant extent, even at the highest concentration studied of 1 mM.