Therapeutic properties, SOD and catecholase mimetic activities of novel ternary copper(II) complexes of the anti-inflammatory drug Fenoprofen with imidazole and caffeine

The copper(II) ternary complexes of the non-steroidal anti-inflammatory drug Fenoprofen (Hfen) and the biologically relevant molecules imidazole (im) and caffeine (caf) as auxiliary ligands were investigated as novel anti-inflammatory agents. The new copper(II) complexes with formula [Cu(fen)2(im)2] (1) and Cu2(fen)4(caf)2 (2) were synthesized from the dinuclear complex [Cu2(fen)4(dmf)2] and characterized by IR, UV–Vis, EPR spectral and elemental analysis. The molecular structure of complex 1 was determined by X-ray crystallography. Both complexes 1 and 2 present enhanced and prolongued anti-inflammatory properties against the parent drug calcium Fenoprofenate, Ca(fen)2·2H2O, with a better performance for complex 1. Ternary complexes are potential models for several mono and poly-nuclear metal enzymes. The measured superoxide dismutase (SOD) mimetic activities of the complexes indicated a higher SOD mimic activity for complex 2 (IC50 of 0.24 μM) than complex 1 (IC50 of 0.70 μM), and also than the native enzyme evaluated by the same method (IC50 of 0.480 μM). The catecholase activity of the complexes toward the aerobic oxidation of 3,5-di-tert-butylcatechol (dtbc) onto 3,5-di-tert-butylquinone (dtbq) showed that both complexes have moderate catalytic oxidase activity.

Anti-inflammatory activity achieved for complexes under study and the corresponding uncomplexed parent drug in carrageenan induced paw oedema in mice.Figure optionsDownload as PowerPoint slideHighlights
► Cu(II) complexes of Fenoprofen with imidazole and caffeine as therapeutic agents.
► Both complexes were characterized employing spectral and biological techniques.
► They present enhanced and lasting anti-inflammatory properties than the parent drug.
► Both complexes show potent superoxide dismutase activity acting as good antioxidants.
► The catechol oxidase activity revealed that they have moderate mimetic properties.