Complexation of the anti-Trypanosoma cruzi Drug Benznidazole Improves Solubility and Efficacy

摘要: The ruthenium complex, trans-[Ru(Bz)(NH3)4SO2](CF3SO3)2 1, Bz = benznidazole (N-benzyl-2-(2-nitro-1H-imidazol-1-yl)acetamide), is more hydrosoluble and active (IC50try/1 h 79 ± 3 μM) than free 2 > 1 mM). also exhibits low acute toxicity in vitro (IC50macrophages mM) vivo (400 μmol/kg < LD50 600 μmol/kg) the formation of hydroxylamine favorable by 9.6 kcal/mol. In murine models Chagas’ disease, was even when only one dose administrated. Moreover, at a thousand-fold smaller concentration considered optimal for (385 μmol/kg/day 100 mg/kg/day), proved to be sufficient protect all infected mice, eliminating amastigotes their hearts skeletal muscles as observed H&E micrographics.