Metal‐based antimicrobial strategies against intramacrophage Mycobacterium tuberculosis

The combinatorial chemistry has been an important tool for the development of new strategies against the Mycobacterium tuberculosis. Therefore, we evaluated the antimycobacterial activity of two coordinated metal complexes (Cu(II) and Co(II)) and a free ligand, including in the intramacrophage environment. The complexes were more active than the free ligand, indicating that the complexation favored the antimicrobial activity. None of the compounds showed cytotoxic effect at the concentration of 200 microg ml(-1) and both complexes showed intracellular antimicrobial activity, with results as effective as rifampicin. In this study, it was possible to identify complexes containing benzohydroxamate associated with transition metal ions (Cu(2+) and Co(2+) ), which were able to inhibit the growth of M. tuberculosis, including in persistence stage. In addition, the docking analysis allows inferring a possible interaction of the metal complexes with the enzyme urease, which has been reported as crucial for the bacillus survival in intraphagosomal environment. Thus, these set of results demonstrate the potential of these metals in the development of new drugs against M. tuberculosis.