Síntese, caracterização e estudo da atividade antitubercular de derivados quinolínicos e seus complexos de cobre(II) e de prata(I)

Abstract

The present work describes the synthesis, characterization and biological activity of five quinolina derivatives, 4,7-DCQ; 4,7-ACQ1,2; 4,7-ACQ1,3; 4,7-ACQ1,4; 4,7-ACQofen and two classes of copper(II) and silver(I) complexes. The class of organic compounds is composed by 4,7-dichloroquinoline, 4,7-DCQ; and derivatives containing aliphatic diamines, 1,2- ethanediamine – 4,7-ACQ1,2; 1,3-propanediamine – 4,7-ACQ1,3; 1,4-butanediamine – 4,7- ACQ1,4; and an aromatic diamine, o-phenylenediamine – 4,7-ACQofen, as a side chain at the 4-position of the quinoline ring, 4,7-ACQ1,2; 4,7-ACQ1,3; 4,7-ACQ1,4; 4,7-ACQofen. The first class of coordination compounds consists of copper(II) complexes and silver(I) complexes with quinoline derivatives, the complexes have been shown a 1:1 (M:L) molar ratio, except Cu4,7DCQ; Ag-4,7DCQ; and Cu-4,7ACQofen complexes, that showed 1:2 (M:L). The second class is composed of heteroleptic silver(I) complexes containing the ligands 4,7-DCQ (L) and bpy or PPh3, with molar ratio of 1:1:1 (M:L: bpy or PPh3). All compounds were analyzed by analytical methods, spectroscopic techniques, and single crystal or polycrystalline X-ray diffraction measurements. The crystalline structures of Cu-4,7DCQ; Ag-4,7DCQ; Agbpy4,7DCQ; AgPPh3-4,7DCQ and 4,7ACQofen were obtained by single crystal X-ray, while the crystal structures of Cu-4,7ACQ1,2; Ag-4,7ACQ1,2; Ag-4,7ACQ1,3; Ag-4,7ACQ1,4 and Ag4,7ACQofen complexes were obtained by polycrystals technique. The results of elemental analyses, conductometry and IR, Raman and UV-VIS spectroscopies, allowed the confirmation of the proposed molecular formulas for all compounds. Indeed, for all synthesized complexes, the coordination occurs through the nitrogen atom of the quinoline ring. In vitro biological assays were performed for all synthesized compounds against Mycobacterium tuberculosis H37Rv (ATCC 27294). The outcome brings that all ligands and copper(II) compounds showed antimycobacterial activity on the evaluated strains, having activity similar to second order drugs. For Ag(I) specifically, Ag-4,7DCQ; AgPPh3-4,7DCQ; Ag-4,7ACQ1,4 and Ag4,7ACQofen complexes showed MIC90 below than 20.00 mg.L-1 which is a promising antimycobacterial activity.