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.
Reguera
R
R
Dpto Fisiología, Farmacología y Toxicología, Ftad de Veterinaria, Universidad de León, Spain.
Balaña Fouce
R
R
Cubria
J C
JC
Alvarez Bujidos
M L
ML
Ordoñez
D
D
D000578:Amidines / Q000494:pharmacology*; D000818:Animals; D004133:Diminazene / Q000031:analogs & derivatives / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D007700:Kinetics; D018314:Leishmania infantum / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D010419:Pentamidine / Q000494:pharmacology; D011700:Putrescine / Q000378:metabolism*; D013266:Stilbamidines / Q000494:pharmacology
D000578:Amidines; D007211:Indoles; D013266:Stilbamidines; C007293:DAPI; D010419:Pentamidine; C003915:diminazene aceturate; C042560:stilbamidine; D011700:Putrescine; D004133:Diminazene