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Metal-based antimicrobial strategies against intramacrophage Mycobacterium tuberculosis.
Coelho, T S; Halicki, P C B; Silva, L; de Menezes Vicenti, J R; Gonçalves, B L; Almeida da Silva, P E; Ramos, D F.
Afiliação
  • Coelho TS; Núcleo de Pesquisa em Microbiologia Médica, Faculdade de Medicina, Universidade Federal do Rio Grande - FURG, Rio Grande, Brazil.
  • Halicki PCB; Núcleo de Pesquisa em Microbiologia Médica, Faculdade de Medicina, Universidade Federal do Rio Grande - FURG, Rio Grande, Brazil.
  • Silva L; Núcleo de Desenvolvimento de Novos Fármacos, Faculdade de Medicina, Universidade Federal do Rio Grande - FURG, Rio Grande, Brazil.
  • de Menezes Vicenti JR; Núcleo de Pesquisa em Microbiologia Médica, Faculdade de Medicina, Universidade Federal do Rio Grande - FURG, Rio Grande, Brazil.
  • Gonçalves BL; Núcleo de Desenvolvimento de Novos Fármacos, Faculdade de Medicina, Universidade Federal do Rio Grande - FURG, Rio Grande, Brazil.
  • Almeida da Silva PE; Escola de Química de Alimentos, Universidade Federal do Rio Grande - FURG, Rio Grande, Brazil.
  • Ramos DF; Escola de Química de Alimentos, Universidade Federal do Rio Grande - FURG, Rio Grande, Brazil.
Lett Appl Microbiol ; 71(2): 146-153, 2020 Aug.
Article em En | MEDLINE | ID: mdl-32286695
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Cobalto / Cobre / Macrófagos / Mycobacterium tuberculosis / Antituberculosos Limite: Humans Idioma: En Revista: Lett Appl Microbiol Assunto da revista: MICROBIOLOGIA Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Brasil País de publicação: Reino Unido
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Cobalto / Cobre / Macrófagos / Mycobacterium tuberculosis / Antituberculosos Limite: Humans Idioma: En Revista: Lett Appl Microbiol Assunto da revista: MICROBIOLOGIA Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Brasil País de publicação: Reino Unido