Complexation of the anti-Trypanosoma cruzi drug benznidazole improves solubility and efficacy
Contribuinte(s) |
UNIVERSIDADE DE SÃO PAULO |
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Data(s) |
20/10/2012
20/10/2012
2008
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Resumo |
The ruthenium complex,trans-[Ru(Bz)(NH3)(4)SO2](CF3SO3)(2) 1, Bz = benznidazole (N-benzyl-2-(2-nitro-1H-imidazol-1-yl)acetamide), is more hydrosoluble and more active (IC50try/1 h = 79 +/- 3 mu M) than free benznidazole 2 (IC50try/1 h > 1 mM). 1 also exhibits low acute toxicity in vitro (IC50macrophages > 1 mM) and in vivo (400 mu mol/kg < LD50 < 600 mu mol/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 mu mol/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. |
Identificador |
JOURNAL OF MEDICINAL CHEMISTRY, v.51, n.14, p.4104-4114, 2008 0022-2623 http://producao.usp.br/handle/BDPI/31744 10.1021/jm701306r |
Idioma(s) |
eng |
Publicador |
AMER CHEMICAL SOC |
Relação |
Journal of Medicinal Chemistry |
Direitos |
restrictedAccess Copyright AMER CHEMICAL SOC |
Palavras-Chave | #CHAGAS-DISEASE #IN-VITRO #TROPICAL DISEASES #NITROIMIDAZOLE DERIVATIVES #BIOLOGICAL-ACTIVITY #NITROSYL COMPLEXES #LIGANDS #AGENTS #MODEL #COORDINATION #Chemistry, Medicinal |
Tipo |
article original article publishedVersion |