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J Inorg Biochem ; 153: 178-185, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26298864

RESUMO

This work presents the synthesis and characterization of two novel binuclear ruthenium compounds of general formula [Ru2O(carb)2(py)6](PF6)2, where py=pyridine and carb are the non-steroidal anti-inflammatory drugs ibuprofen (1) and ketoprofen (2). Both complexes were characterized by ESI-MS/MS spectrometry. The fragmentation patterns, which confirm the proposed structures, are presented. Besides that, compounds 1 and 2 present the charge transfer transitions within 325-330nm; and the intra-core transitions around 585nm, which is the typical spectra profile for [Ru2O] analogues. This suggests the carboxylate bridge has little influence in their electronic structure. The effects of the diruthenium complexes on Ig-E mediated mast cell activation were evaluated by measuring the enzyme ß-hexosaminidase released by mast cells stimulated by antigen. The inhibitory potential of the ketoprofen complex against mast cell stimulation suggests its promising application as a therapeutic agent for treating or preventing IgE-mediated allergic diseases. In addition, in vitro metabolism assays had shown that the ibuprofen complex is metabolized by the cytochrome P450 enzymes.


Assuntos
Antialérgicos/farmacologia , Complexos de Coordenação/farmacologia , Ibuprofeno/farmacologia , Cetoprofeno/farmacologia , Rutênio/química , Animais , Antialérgicos/síntese química , Antialérgicos/química , Degranulação Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Sistema Enzimático do Citocromo P-450/metabolismo , Ibuprofeno/síntese química , Ibuprofeno/química , Imunoglobulina E/imunologia , Cetoprofeno/síntese química , Cetoprofeno/química , Masculino , Mastócitos/efeitos dos fármacos , Mastócitos/imunologia , Mastócitos/metabolismo , Microssomos Hepáticos/metabolismo , Ratos , Ratos Wistar , Espectrometria de Massas por Ionização por Electrospray , beta-N-Acetil-Hexosaminidases/antagonistas & inibidores
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