Nitrosilocomplexos e isoniazida: reatividade e potencial biológico

Abstract

The combined use of bioactive compounds, as well as the positive or negative effects of their reactivities, has been reported in the literature, including a synergistic effect between nitric oxide and antituberculosis drugs, such as isoniazid, potentiating bactericidal activity. In this work we investigated the reactivity of nitrosylocomplexes, cis-[Ru(bpy)2(L)(NO)]n+ , where L = imidazole, 1-methylimidazole, thiourea and sulfite, and [Fe(CN)5NO]2- , with isoniazid, in order to try to elucidate the products of this reaction and generated reactive species, as well as to evaluate possible biological activities improved. In this study, chromatographic, spectroscopic and electrochemical techniques were used to monitor these reactions, showing a reduction of the nitrosyl group and its labilization of the metallic center, with the subsequent formation of a corresponding aquacomplex. In addition, the formation of other ruthenium bipyridine complexes in the reaction medium containing isoniazid and isonicotinic acid was observed, reinforcing the oxidation of isoniazid. Measurements of mass spectrometry were further employed in the identification of products of this reaction, such as ammonia and isonicotinic acid. Additionally, it was observed that the reactivity of the nitrosylocomplexes to the isoniazid followed the electrophilic character of the coordinated NO+. The measurements performed by electronic paramagnetic resonance (EPR) confirmed the release of HNO during the reaction involving cis-[Ru(bpy)2SO3NO]+ with isoniazid. Preliminary biological assays have argued that this combination promotes improved anticancer and vasodilatory activities. Thus, this work demonstrates the reduction capacity of isoniazid against the studied nitrosylcomplexes, originating biologically relevant species, sustaining a possible application of the therapeutic combination of isoniazid and metalonitrosilos.