NITRO ARYL 1,4-DIHYDROPYRIDINE DERIVATIVES - EFFECTS ON TRYPANOSOMA-CRUZI

A series of nitro aryl 1,4-dihydropyridine derivatives produced inhibi tion of both cell growth and oxygen consumption on Tulahuen and LQ str ains, and clone Dm 28c of epimastigotes of Trypanosoma cruzi. Nicardip ine was found to be the most potent derivative in both growth cell (I- 50 = 70 mu M) and oxygen uptake (I-50 = 26 mu M in intact parasites, I -50 = 325 mu M in situ mitochondria). A correlation between the inhibi tory effects on the growth cell and the apparent first order kinetic f or the uptake of the 1,4-dihypyridine derivatives by T. cruzi epimasti gotes was found. Thus, nicardipine, the most potent derivative, exhibi ted the highest apparent rate constant, k(u), (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. (C) 1997 Elsevier Science Inc .