New Ag(I), Pd(II) and Pt(II) metal complexes with ligands used for the treatment of Tuberculosis: synthesis and in vitro evaluation of antimicrobial and antiproliferative activities

Abstract

The increasing bacterial resistance to antibiotics is a global concern that urges the development of new drugs to treat serious infections. Tuberculosis is caused by the bacteria Mycobacterium tuberculosis. One of the reasons for the high mortality number caused by tuberculosis is the emergence of many new bacterial stains that are multiresistant to first line commercial drugs. One strategy to fight multiresistant bacteria is to coordinate well-known drugs to a metal ion with antibacterial activity, resulting in a coordination compound that would have additive or synergic activity with the ligand. Metal complexes with Ag(I) or Pt(II) ions are known for their antibacterial and antitumoral properties, that can be exemplified by silver sulphadiazine, used for the treatment of skin bacterial infections, and cisplatin, used for Cancer chemotherapy and that also has considerable antimicrobial activity. These and other metal ions have been considered for the development of new complexes as lead drugs by research groups. In that context, this project aims at the synthesis, optimization and characterization of new Ag(I), Pd(II) and Pt(II) complexes using as ligand the drugs D-cycloserine and kanamycin A, that are used for Tuberculosis therapy, and also some derivatives of anthranilic acid that have high activity against Mycobacterium tuberculosis. The activity of the complexes against Mycobacterium tuberculosis, as well as the inhibition of eukaryotic cells proliferation using tumoral and non-tumoral cell lines will be evaluated. Furthermore, in this project we also envisage the study of the interaction of the complexes with some biomolecules to suggest their biological mechanism of action. With these assays we hope to determine the pharmacological potential of Ag(I), Pt(II) and Pd(II) complexes to treat severe infectious diseases, as Tuberculosis, and also for Cancer chemotherapy. (AU)