Effects of cationic diamidines on polyamine content and uptake on Leishmania infantum in in vitro cultures.
The effect of a series of cationic diamidines recently synthesized by Ciba Geigy, bearing diarylic (CGP040215A and CGP039937A) or monoarylic moieties (CGP033829A, CGP035537A and CGP036958A), was analyzed on some metabolic targets and cell proliferation of in vitro cultures of Leishmania infantum promastigotes (insect form). The action of these compounds on intracellular polyamine pools and putrescine transport suggests that diarylic structures were more effective than their monoarylic counterparts in depleting polyamine levels and inhibiting putrescine transport, although these processes correlate poorly with the antiproliferative rate of these compounds. Finally, the displacement of cationic diamidines to kDNA observed in the presence of several concentrations of spermidine suggests a possible combined mode of action of these molecules, first depleting intracellular polyamine pools and, then, displacing spermidine from its site of interaction to kDNA.
Calonge
M
M
Departmento de Fisiología, Farmacología y Toxicología, Universidad de León, Spain.
Johnson
R
R
Balaña-Fouce
R
R
Ordóñez
D
D
D000818:Animals; D015317:Biogenic Polyamines / Q000378:metabolism*; D002412:Cations; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D018314:Leishmania infantum / Q000187:drug effects*; D010419:Pentamidine / Q000494:pharmacology*; D013095:Spermidine / Q000378:metabolism
D015317:Biogenic Polyamines; D002412:Cations; D010419:Pentamidine; D013095:Spermidine