Metal complexes of sulfonamides : synthesis, characterization and biological activities = Complexos metálicos de sulfonamidas: síntese, caracterização e atividades biológicas: Complexos metálicos de sulfonamidas : síntese, caracterização e atividades biológicas

Abstract: Metal complexes are a promising class of molecules for the development of new (metallo)drugs, since their properties can be modulated with the modifications of parameters, like the nature of the metal ion and of the ligands. Sulfonamides are one class of versatile molecules to use as ligands for the design of new metallodrugs. In this context, the objectives of this Thesis are the preparation of new metal complexes of sulfonamides, the study of their interactions with biomolecules (potential targets) and the correlation of chemical and structural properties with the bioactivities of the synthesized molecules. As results, two new silver(I) complexes and three copper(II) complexes of the sulfonamides sulfameter and sulfadimethoxine were prepared. Additionally, the 4-(2-aminoethyl)-benzenesulfonamide was used as ligand for the preparation of two novel platinum(II) complexes, two Schiff bases and two palladium(II) complexes of such Schiff bases. All molecules were characterized by chemical and spectroscopic techniques and most of them had their crystal structures solved from X-ray diffraction data. The silver(I) complexes were active over three bacterial strains on the micromolar range. Their incorporation in bacterial cellulose membranes resulted in devices capable of releasing the active compounds for three days, so that such devices could be further developed as topical wound dressings. The copper(II) complexes behaved as artificial nucleases and were active over Mycobacterium tuberculosis and some cancer cell lines, in a way that the sulfonamide ligand modulated the activity of the compounds. The palladium(II) and platinum(II) compounds were able to alter DNA secondary structure, which is usually the main target of such metallodrugs. Overall, the metal complexes synthesized in this Thesis demonstrated the potential of combining sulfonamides to metal ions for the development of new and promising metallodrugs