Enhanced analgesic properties and reduced ulcerogenic effect of a mononuclear copper(II) complex with Fenoprofen in comparison to the parent drug. Promising insights in the treatment of chronic inflammatory diseases?

MARIELA A. AGOTEGARAY; FERNANDA A. GUMILAR; MÓNICA A. BOERIS; RICARDO E. TOSO; ALEJANDRA MINETTI

BioMed Research International

HINDAWI PUBLISHING CORPORATION

Año: 2014 vol. 2014 p. 1 - 9

2314-6133

Analgesic and ulcerogenic properties have been studied for the copper(II) coordination complex of the nonsteroidal antiinflammatory drug Fenoprofen and the biologically active molecule imidazole with the formula [Cu(fen)2(im)2] (where Cu: copper(II) ion; fen: fenoprofenate anion from Fenoprofen acidic form; im: imidazole). In all assays, a therapeutic dose of 28mg/kg was tested for [Cu(fen)2(im)2] and a dose of 21 mg/kg was employed for Fenoprofen calcium salt, administered by oral gavage in female mice in order to compare the therapeutic properties of the new entity and the commercial parent drug. The acetic acidinduced writhing test was employed in vivo in mice for the study of visceral pain. Results revealed that the percentage of inhibition in writhing and stretching was 78.9% and 46.2% for the [Cu(fen)2(im)2] complex and Fenoprofen calcium salt, respectively. This result indicates that the complex could bemore effective in diminishing visceral pain than the uncomplexed drug.The formalin test was evaluated in mice in order to study the impact of the drugs studied over nociceptive and inflammatory pain. Results revealed that the complex is amore potent analgesic on inflammatory pain than the parent drug, Fenoprofen calciumsalt.Ulcerogenic effects were evaluated using a model of gastric lesions induced by hypothermic-restraint stress. Fenoprofen calcium salt caused an ulcer index of about 79mm2 while the one caused by [Cu(fen)2(im)2] was found to be 22mm2. This study revealed that the complex diminished the development of gastric mucosal ulcers in comparison to the uncomplexed parent drug. Possible mechanisms of action related to both therapeutic properties studied have been discussed. The presence of copper(II) ion in the complex moiety may become crucial for the enhanced therapeutic properties of [Cu(fen)2(im)2] in comparison to uncomplexed Fenoprofen.