Synthesis, spectroscopic and DFT structural characterization of two novel ruthenium(III) oxicam complexes. In vivo evaluation of anti-inflammatory and gastric damaging activities

reactions of ruthenium(III) chloride trihydrate with piroxicam (H2PIR) and tenoxicam (H2TEN), two widely used non-steroidal anti-inflammatory drugs, afforded [(RuCl2)-Cl-III(H2PIR)(HPIR)],center dot 1, and [(RuCl2)-Cl-III(H2TEN)(HTEN)],center dot 2. Both compounds were obtained as pure green solids through purification via flash column chromatography. Characterizations were accomplished through UV-vis and IR spectroscopy, potentiometry and HPLC. Quantum mechanics and density functional computational methods were applied to investigate their respective molecular structures. The experimental and computational results are in agreement with a pseudo-octahedral coordination where the two chlorido ligands are in trans positions (apical) and the two trans-N,O chelating oxicam ligands occupy the equatorial sites. Both compounds revealed an acceptable solubility and stability profile upon dissolution in a standard buffer at physiological pH. Nonetheless, the addition of biologically occurring reducing agents caused spectral changes. The two complexes manifested a poor reactivity with the model proteins cytochrome c and lysozyme: no evidence for adduct formation was indeed obtained based on a standard ESI MS analysis; in contrast, some significant reactivity with serum albumin was proved spectrophotometrically. Remarkably, both study compounds revealed pronounced anti-edema effects in vivo suggesting that the pharmacological actions of the ligands are mostly retained; in addition, they were less irritating than piroxicam on the gastric mucosa when the coordination compounds and free oxicam were administered at the same overall molar concentration of the ligand. Overall, the present results point out that ruthenium coordination may represent an effective strategy to improve the pharmacological properties of oxicam drugs reducing their undesired side effects. (c) 2014 Elsevier Inc. All rights reserved.