title: Novel binuclear μ-oxo diruthenium complexes combined with ibuprofen and ketoprofen: Interaction with relevant target biomolecules and anti-allergic potential.
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 β-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.
authors: Departamento de Química, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Av. Bandeirantes 3900, 14040-901 Ribeirão Preto -SP, Brazil.
authors: Gabriela Campos
authors: GC
authors: Seuanes
authors: Departamento de Química, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Av. Bandeirantes 3900, 14040-901 Ribeirão Preto -SP, Brazil.
authors: Mariete Barbosa
authors: MB
authors: Moreira
authors: Departamento de Química, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Av. Bandeirantes 3900, 14040-901 Ribeirão Preto -SP, Brazil.
authors: Tânia
authors: T
authors: Petta
authors: Departamento de Física e Química da Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Av. do Café s/n, 14040-903 Ribeirão Preto, São Paulo, Brazil; Instituto Nacional de Ciência e Tecnologia de Bioanalítica, Campinas 13083-970, Brazil.
authors: Maria Perpétua Freire
authors: MPF
authors: de Moraes Del Lama
authors: Departamento de Química, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Av. Bandeirantes 3900, 14040-901 Ribeirão Preto -SP, Brazil.
authors: Luiz Alberto Beraldo
authors: LAB
authors: de Moraes
authors: Departamento de Química, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Av. Bandeirantes 3900, 14040-901 Ribeirão Preto -SP, Brazil.
authors: Anderson Rodrigo Moraes
authors: ARM
authors: de Oliveira
authors: Departamento de Física e Química da Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Av. do Café s/n, 14040-903 Ribeirão Preto, São Paulo, Brazil; Instituto Nacional de Ciência e Tecnologia de Bioanalítica, Campinas 13083-970, Brazil. Electronic address: rmzgnaal@fcfrp.usp.br.
authors: Rose Mary Zumstein Georgetto
authors: RMZG
authors: Naal
authors: Departamento de Química, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Av. Bandeirantes 3900, 14040-901 Ribeirão Preto -SP, Brazil. Electronic address: sofia@ffclrp.usp.br.
authors: Sofia
authors: S
authors: Nikolaou
mesh_terms: D000818:Animals; D018926:Anti-Allergic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015550:Cell Degranulation / Q000187:drug effects; D045744:Cell Line, Tumor; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D007052:Ibuprofen / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D007073:Immunoglobulin E / Q000276:immunology; D007660:Ketoprofen / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008862:Microsomes, Liver / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012428:Ruthenium / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization; D001619:beta-N-Acetylhexosaminidases / Q000037:antagonists & inhibitors
chemical_list: D018926:Anti-Allergic Agents; D056831:Coordination Complexes; D007073:Immunoglobulin E; D012428:Ruthenium; D003577:Cytochrome P-450 Enzyme System; D007660:Ketoprofen; D001619:beta-N-Acetylhexosaminidases; D007052:Ibuprofen
keywords: Antiallergic potential; Binuclear ruthenium compounds; Cytochrome P450 enzymes; Ibuprofen; IgE-mediated allergic diseases; Ketoprofen