Antioxidant Activity of Ruthenium Complexes Containing Nitro‐imidazole Derivatives

Abstract

Ruthenium‐based coordination complexes are compounds with great pharmacological potential. Once their toxicity and pharmacokinetics properties can be easily modulated changing the ligands on the six coordination sites of the metal, those species can present a broad spectrum of applications, such as: antineoplastic, bactericide, antiparasitic, vasorelaxant, among others. However, antioxidant properties of that kind of substance is still poorly explored, even after recent works have shown evidence that nitrosyl ruthenium complexes can scavenger free radicals. In addition, nitro‐imidazole derivatives are organic compounds with antioxidant properties and are able to work as ligands in coordination complexes. Considering that, the compounds cis‐[Ru(NO2)(bpy)2(4NIMN)](PF6) (1) and cis‐[RuCl(bpy)2(MTZ)](PF6) (2), where bpy=2,2′‐bipyridine, 4NIMN=4‐nitroimidazole and MTZ=metronidazole, were selected for analysis. Thus, the aim of the present study was to investigate in vitro antioxidant activity of those ruthenium complexes. The complexes were synthesized using microwave‐assisted synthesis, adapting methods previously described. Structural characterization was held through spectroscopic and spectrometric techniques, confirming the proposed structures. Cytotoxicity of the compounds at 3.12 to 100.0 μM was evaluated on A549 human lung carcinoma, RAW 264.7 murine macrophages, AGS human gastric carcinoma cells and human neutrophils at 5×106 cells/mL. No significant cytotoxicity was observed at any concentration of the compounds. Antioxidant properties were evaluated by quantifying malondialdehyde (MDA) and reactive oxygen species (ROS) production, and by evaluating superoxide dismutase activity in LPS‐stimulated RAW 264.7 cells treated with 1 and 2 at 3 – 25 μM. All the concentrations of both complexes were able to significantly reduce the production of superoxide anion in relation to the vehicle group, similarly to the reference treatment (α – tocopherol) All concentrations could also reduce the amount of MDA and ROS produced. Finally, the ruthenium complexes 1 and 2 were not cytotoxic to human neutrophils, lung and gastric carcinomas, and presented potent antioxidant properties. Tests are being carried out in order to elucidate antioxidant mechanisms and to analyze possible anti‐inflammatory effects.Support or Funding InformationCAPES; CNPqThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.