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J Inorg Biochem ; 153: 178-185, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26298864

ABSTRACT

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.


Subject(s)
Anti-Allergic Agents/pharmacology , Coordination Complexes/pharmacology , Ibuprofen/pharmacology , Ketoprofen/pharmacology , Ruthenium/chemistry , Animals , Anti-Allergic Agents/chemical synthesis , Anti-Allergic Agents/chemistry , Cell Degranulation/drug effects , Cell Line, Tumor , Coordination Complexes/chemical synthesis , Coordination Complexes/chemistry , Cytochrome P-450 Enzyme System/metabolism , Ibuprofen/chemical synthesis , Ibuprofen/chemistry , Immunoglobulin E/immunology , Ketoprofen/chemical synthesis , Ketoprofen/chemistry , Male , Mast Cells/drug effects , Mast Cells/immunology , Mast Cells/metabolism , Microsomes, Liver/metabolism , Rats , Rats, Wistar , Spectrometry, Mass, Electrospray Ionization , beta-N-Acetylhexosaminidases/antagonists & inhibitors
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