Isoniazida funcionalizada com aldeídos naturais e seus respectivos complexos de prata(I): síntese, caracterização e estudo da atividade contra Mycobacterium tuberculosis

Abstract

In the present work, the syntheses, characterizations, and biological studies of Nacylhydrazones: IZBEN, IZxSAL, IZxAN, IZxNIT, IZxVA, IZCIN (where x: ortho, meta and para positions in the benzene ring) and N-acylhydrazines: IZBEN-Red, IZoSAL-Red and IZoVA-Red, are described. At the same time, the respective silver(I) complexes were synthesized, in the ratio 1:2 (M:L) and 1:1 (M:L). All compounds were analyzed by analytical methods, spectroscopic techniques, such as 1H and 13C NMR and by X-ray diffraction. Only crystalline strucuture of complex [Ag(IZoVA)2(NO3)]·H2O was solved, using the polycrystalline method. To all synthesized complexes, the coordination of ligands occurs through the nitrogen atom of the pyridine ring, as shown IR and 1H and 13C spectroscopic studies, even for the complexes that the crystalline structures were not solved. Also, the crystalline structure of N-acylhydrazine IZoVA-Red has been solved by single-crystal X-ray diffraction method. In vitro biological tests were carried out for all synthesized compounds, in which the minimum inhibitory concentration (MIC90) of the compounds against Mycobacterium tuberculosis H37Rv (ATCC 27294) was determined. Biological outcomes state that most of the compounds showed relevant antimycobacterial activity. Furthermore, silver(I) complexes have higher antimicrobial response against Mtb than respective ligands. The complexes AgIZoSAL, AgIZpVA, AgIZmVA, AgIZoVA, AgIZoNIT and AgIZpAN showed MIC90 values between <0.098 and 1.08 mg L–1