RESUMO
The ruthenium complex, trans-[Ru(Bz)(NH 3) 4SO 2](CF 3SO 3) 2 1, Bz = benznidazole ( N-benzyl-2-(2-nitro-1 H-imidazol-1-yl)acetamide), is more hydrosoluble and more active (IC 50try/1 h = 79 +/- 3 microM) than free benznidazole 2 (IC 50try/1 h > 1 mM). 1 also exhibits low acute toxicity in vitro (IC 50macrophages > 1 mM) and in vivo (400 micromol/kg < LD 50 < 600 micromol/kg) and the formation of hydroxylamine is more favorable in 1 than in 2 by 9.6 kcal/mol. In murine acute models of Chagas' disease, 1 was more active than 2 even when only one dose was administrated. Moreover, 1 at a thousand-fold smaller concentration than the considered optimal dose for 2 (385 micromol/kg/day = 100 mg/kg/day), proved to be sufficient to protect all infected mice, eliminating the amastigotes in their hearts and skeletal muscles as observed in H&E micrographics.
Assuntos
Nitroimidazóis/farmacologia , Tripanossomicidas/farmacologia , Trypanosoma cruzi/efeitos dos fármacos , Animais , Doença de Chagas/tratamento farmacológico , Modelos Animais de Doenças , Espectroscopia de Ressonância Magnética , Camundongos , Camundongos Endogâmicos BALB C , Nitroimidazóis/química , Nitroimidazóis/uso terapêutico , Espectrofotometria Ultravioleta , Tripanossomicidas/química , Tripanossomicidas/uso terapêuticoRESUMO
Electrochemical and spectrophotometric methods are described for measuring the rate of nitric oxide (NO) dissociation (k(NO)) from coordination compounds. Electrochemical methods based on double-potential step chronoamperometry and rotating ring-disc electrode voltammetry techniques proved to be suitable for measuring NO dissociation from 0.03 to 4.0 s(-1). The spectrophotometric method using an ancillary ligand as a colorimetric indicator is illustrated on measuring k(-NO)=0.002 s(-1). This methodology is limited only by the rate of the ancillary ligand substitution.
