Novel binuclear μ-oxo diruthenium complexes combined with ibuprofen and ketoprofen: Interaction with relevant target biomolecules and anti-allergic potential

• Published in: Journal of inorganic biochemistry Vol. 153; pp. 178 - 185
• Main Authors: Seuanes, Gabriela Campos, Moreira, Mariete Barbosa, Petta, Tânia, de Moraes Del Lama, Maria Perpétua Freire, de Moraes, Luiz Alberto Beraldo, de Oliveira, Anderson Rodrigo Moraes, Naal, Rose Mary Zumstein Georgetto, Nikolaou, Sofia
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-12-2015
• Subjects: Animals; Anti-Allergic Agents - chemical synthesis; Anti-Allergic Agents - chemistry; Anti-Allergic Agents - pharmacology; Antiallergic potential; beta-N-Acetylhexosaminidases - antagonists & inhibitors; Binuclear ruthenium compounds; Cell Degranulation - drug effects; Cell Line, Tumor; Coordination Complexes - chemical synthesis; Coordination Complexes - chemistry; Coordination Complexes - pharmacology; Cytochrome P-450 Enzyme System - metabolism; Cytochrome P450 enzymes; Ibuprofen; Ibuprofen - chemical synthesis; Ibuprofen - chemistry; Ibuprofen - pharmacology; IgE-mediated allergic diseases; Immunoglobulin E - immunology; Ketoprofen; Ketoprofen - chemical synthesis; Ketoprofen - chemistry; Ketoprofen - pharmacology; Male; Mast Cells - drug effects; Mast Cells - immunology; Mast Cells - metabolism; Microsomes, Liver - metabolism; Rats; Rats, Wistar; Ruthenium - chemistry; Spectrometry, Mass, Electrospray Ionization; Antiallergic potential; Cytochrome P450 enzymes; Binuclear ruthenium compounds; IgE-mediated allergic diseases; Ketoprofen; Ibuprofen
• ISSN: 0162-0134; 1873-3344
• DOI: 10.1016/j.jinorgbio.2015.08.004

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.
Synthesis and structural characterization of novel binuclear ruthenium compounds [Ru2O(carb)2(py)6](PF6)2, (py=pyridine; carb=ibuprofen 1 and ketoprofen 2) are reported. Compound 1 is metabolized by the cytochrome P450 enzymes, while compound 2 inhibits mast cell activation, suggesting its promising application as a therapeutic agent for treating or preventing IgE-mediated allergic diseases. [Display omitted]
•Compounds [Ru2O(carb)2(py)6](PF6)2 (carb=ibuprofen or ketoprofen) are reported.•Their structures were characterized by ESI MS/MS spectrometry.•[Ru2O(ibu)2(py)6](PF6)2 is metabolized by the cytochrome P450 enzymes.•[Ru2O(keto)2(py)6](PF6)2 inhibits mast cell activation.•[Ru2O(keto)2(py)6](PF6)2 showed a pronounced anti-allergic potential.