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

作者:Seuanes Gabriela Campos; Moreira Mariete Barbosa; Petta Tania; Freire de Moraes Del Lama Maria Perpetua; Beraldo de Moraes Luiz Alberto; Moraes de Oliveira Anderson Rodrigo; Zumstein Georgetto Naal Rose Mary; Nikolaou Sofia
来源:Journal of Inorganic Biochemistry, 2015, 153: 178-185.
DOI:10.1016/j.jinorgbio.2015.08.004

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.

  • 出版日期2015-12