Síntese, caracterização e estudos de reatividade do complexo cis-[Ru(bpy)2(mbpy-izd)]2+: uma proposta de fármaco anti-tuberculose

Abstract

This work presents the synthesis, characterization and reactivity studies of a new ruthenium polypyridine complex containing a bipyridine ligand modified with the pro-drug isoniazid, cis-[Ru (bpy)2(mbpy-izd)]2+ (Ru-izd). This proposal expects to create a photoactivatable system of isoniazid by taking advantage of the photogeneration of radical oxidizing species. The synthesis of this complex was optimized by high performance liquid chromatography (HPLC), characterized by spectroscopic techniques, electrochemistry, mass spectrometry, elemental analysis and Hydrogen Nuclear Magnetic Resonance (1H NMR). Reactivity studies were carried out investigating the stability at different pH values, photogeration of radical species, photochemical stability and biological activity against Mycobacterium tuberculosis and Gram positive and negative bacteria. The obtained results were consistent with the proposed formulation of the complex along with an expressive level of purity. Photochemical studies indicate photo activation of this complex, with formation of an oxidized end product in the form of isonicotinic acid, suggesting formation of intermediate active species. The reactivity studies also suggest that the complex presents satisfactory stability at pH 4 to 12, but it decomposes at pH below 3. Biological assays performed on Mycobacterium tuberculosis revealed encouraging results, with 18-fold improved activity if compared to the precursor complex as measured without proper light protection. In the studies conducted with Gram positive and negative bacteria, both bactericidal (MBC) and bacteriostatic (MIC) biological activity were observed only for the Ru-izd complex and under light irradiation conditions, which strengthens the perspective of its performance as a possible photoactivatable drug.