Structural Determinants of Putrescine Uptake Inhibition Produced by Cationic Diamidines in the Model of TrypanosomatidCrithidia fasciculata

Abstract

The effect of a heterologous series of cationic diamidines has been tested on cell growth and polyamine uptake on the model of insect Trypanosomatid Crithidia fasciculata. The maximum inhibitory effect on both parameters was found for pentamidine and dibromopropamidine, which exhibit a longer distance between amino and imino substituents. A minimum inhibitory effect was found with amicarbalide. A good relationship was obtained when the distance between amino moieties was plotted versus the inhibitory effect on putrescine uptake, suggesting a role of this structural property on polyamine transport in Crithidia fasciculata. In addition, a similar correlation was obtained for another Trypanosomatid parasite, Leishmania infantum.

Diamidine Compounds: Selective Uptake and Targeting inPlasmodium falciparum

“…Pentamidine is known to inhibit several transport systems on the surface of eukaryotic cells (Kandpal et al, 1995;Kleyman et al, 1995;Navas et al, 1996;de Koning and Jarvis, 1999). It is possible that pentamidine may exert its antimalarial effect by inhibiting the transport of essential nutrients or metabolites across the host erythrocyte membrane.…”