Metal‐based antimicrobial strategies against intramacrophage Mycobacterium tuberculosis

• Published in: Letters in applied microbiology Vol. 71; no. 2; pp. 146 - 153
• Main Authors: Coelho, T.S., Halicki, P.C.B., Silva, L., Menezes Vicenti, J.R., Gonçalves, B.L., Almeida da Silva, P.E., Ramos, D.F.
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01-08-2020
• Subjects: Antiinfectives and antibacterials; Antimicrobial activity; Antimicrobial agents; antimycobacterial; Carbon dioxide; Cobalt; cobalt(II); Combinatorial analysis; Combinatorial chemistry; Coordination compounds; Copper; copper(II); Cytotoxicity; Drug development; Drugs; Heavy metals; Ligands; Metal complexes; Metal ions; metallodrugs; Mycobacterium tuberculosis; Rifampin; Transition metals; Tuberculosis; Urease; antimycobacterial; copper(II); metallodrugs; cobalt(II); tuberculosis
• ISSN: 0266-8254; 1472-765X
• DOI: 10.1111/lam.13298

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 favoured the antimicrobial activity. None of the compounds showed cytotoxic effect at the concentration of 200 µg 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 (Cu2+ and Co2+), 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 the intraphagosomal environment. Thus, these set of results demonstrate the potential of these metals in the development of new drugs against M. tuberculosis.
Significance and Impact of the Study
In this study, it was possible to identify complexes containing benzohydroxamate associated with transition metals (Cu2+ and Co2+), which were able to inhibit the growth of Mycobacterium tuberculosis, including in the persistence stage. In this context, cobalt and copper can be scaffolds for new drugs against M. tuberculosis.
Significance and Impact of the Study: In this study, it was possible to identify complexes containing benzohydroxamate associated with transition metals (Cu2+ and Co2+), which were able to inhibit the growth of Mycobacterium tuberculosis, including in the persistence stage. In this context, cobalt and copper can be scaffolds for new drugs against M. tuberculosis.