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

摘要

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 325-330 nm; and the intra-core transitions around 585 nm, 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 beta-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. (C) 2015 Elsevier Inc. All rights reserved.