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J Inorg Biochem ; 153: 178-185, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26298864

RESUMEN

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.


Asunto(s)
Antialérgicos/farmacología , Complejos de Coordinación/farmacología , Ibuprofeno/farmacología , Cetoprofeno/farmacología , Rutenio/química , Animales , Antialérgicos/síntesis química , Antialérgicos/química , Degranulación de la Célula/efectos de los fármacos , Línea Celular Tumoral , Complejos de Coordinación/síntesis química , Complejos de Coordinación/química , Sistema Enzimático del Citocromo P-450/metabolismo , Ibuprofeno/síntesis química , Ibuprofeno/química , Inmunoglobulina E/inmunología , Cetoprofeno/síntesis química , Cetoprofeno/química , Masculino , Mastocitos/efectos de los fármacos , Mastocitos/inmunología , Mastocitos/metabolismo , Microsomas Hepáticos/metabolismo , Ratas , Ratas Wistar , Espectrometría de Masa por Ionización de Electrospray , beta-N-Acetilhexosaminidasas/antagonistas & inhibidores
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