Experimental chemotherapy against Trypanosoma cruzi infection using ruthenium nitric oxide donors.

The ruthenium NO donors of the group trans-[Ru(NO)(NH3)4L]n+, where the ligand (L) is N-heterocyclic H2O, SO(3)(2-), or triethyl phosphite, are able to lyse Trypanosoma cruzi in vitro and in vivo. Using half-maximal (50%) inhibitory concentrations against bloodstream trypomastigotes (IC50try) and cytotoxicity data on mammalian V-79 cells (IC50V79), the in vitro therapeutic indices (TIs) (IC50V79/IC50try) for these compounds were calculated. Compounds that exhibited an in vitro TI of > or = 10 and trypanocidal activity against both epimastigotes and trypomastigotes with an IC50(try/epi) of < or = 100 microM were assayed in a mouse model for acute Chagas' disease, using two different routes (intraperitoneal and oral) for drug administration.