Nitro aryl 1,4-dihydropyridine derivatives: effects on Trypanosoma cruzi.
A series of nitro aryl 1,4-dihydropyridine derivatives produced inhibition of both cell growth and oxygen consumption on Tulahuen and LQ strains, and clone Dm 28c of epimastigotes of Trypanosoma cruzi. Nicardipine was found to be the most potent derivative in both growth cell (I50 = 70 microM) and oxygen uptake (I50 = 26 microM in intact parasites, I50 = 325 microM in situ mitochondria). A correlation between the inhibitory effects on the growth cell and the apparent first order kinetic for the uptake of the 1,4-dihypyridine derivatives by T. cruzi epimastigotes was found. Thus, nicardipine, the most potent derivative, exhibited the highest apparent rate constant, ku, (0.043 min-1). On the other hand, no susceptibility differences by strains and clone Dm 28c to the action of these drugs were found.
Núñez-Vergara
L J
LJ
Laboratory of Bioelectrochemistry, Faculty of Chemical and Pharmaceutical Sciences, University of Chile, Santiago, Chile.
Squella
J A
JA
Bollo-Dragnic
S
S
Morello
A
A
Repetto
Y
Y
Aldunate
J
J
Letelier
M E
ME
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004095:Dihydropyridines / Q000494:pharmacology*; D006131:Growth Inhibitors / Q000494:pharmacology; D009529:Nicardipine / Q000494:pharmacology; D009574:Nitro Compounds / Q000494:pharmacology*; D010101:Oxygen Consumption / Q000187:drug effects*; D014349:Trypanosoma cruzi / Q000187:drug effects* / Q000254:growth & development
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D006131:Growth Inhibitors; D009574:Nitro Compounds; D009529:Nicardipine