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Antitubercular activity of Ru (II) isoniazid complexes.
Aguiar, Inara de; Tavares, Aline; Roveda, Antonio C; da Silva, Augusto C H; Marino, Leonardo B; Lopes, Érica O; Pavan, Fernando R; Lopes, Luiz G F; Franco, Douglas W.
Afiliação
  • Aguiar Id; Instituto de Química, Universidade de São Paulo, São Carlos, SP 13566-590, Brazil.
  • Tavares A; Instituto de Química, Universidade de São Paulo, São Carlos, SP 13566-590, Brazil.
  • Roveda AC; Instituto de Química, Universidade de São Paulo, São Carlos, SP 13566-590, Brazil.
  • da Silva AC; Instituto de Química, Universidade de São Paulo, São Carlos, SP 13566-590, Brazil.
  • Marino LB; Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista "Julio de Mesquita Filho", Araraquara, SP 14801-902, Brazil.
  • Lopes ÉO; Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista "Julio de Mesquita Filho", Araraquara, SP 14801-902, Brazil.
  • Pavan FR; Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista "Julio de Mesquita Filho", Araraquara, SP 14801-902, Brazil.
  • Lopes LG; Departamento de Química Orgânica e Inorgânica, Universidade Federal do Ceará, Fortaleza, CE 60455-970, Brazil.
  • Franco DW; Instituto de Química, Universidade de São Paulo, São Carlos, SP 13566-590, Brazil. Electronic address: douglas@iqsc.usp.br.
Eur J Pharm Sci ; 70: 45-54, 2015 Apr 05.
Article em En | MEDLINE | ID: mdl-25638418
Despite the resistance developed by the Mycobacterium tuberculosis (MTb) strains, isoniazid (INH) has been recognized as one of the best drug for treatment of Tuberculosis (Tb). The coordination of INH to ruthenium metal centers was investigated as a strategy to enhance the activity of this drug against the sensitive and resistant strains of MTb. The complexes trans-[Ru(NH3)4(L)(INH)](2+) (L=SO2 or NH3) were isolated and their chemical and antituberculosis properties studied. The minimal inhibitory concentration (MIC) data show that [Ru(NH3)5(INH)](2+) was active in both resistant and sensitive strains, whereas free INH (non-coordinated) showed to be active only against the sensitive strain. The coordination of INH to the metal center in both [Ru(NH3)5(INH)](2+) and trans-[Ru(NH3)4(SO2)(INH)](2+) complexes led to a shift in the INH oxidation potential to less positive values compared to free INH. Despite, the ease of oxidation of INH did not lead to an increase in the in vitro INH activity against MTb, it might have provided sensitivity toward resistant strains. Furthermore, ruthenium complexes with chemical structures analogous to those described above were synthesized using the oxidation products of INH as ligands (namely, isonicotinic acid and isonicotinamide). These last compounds were not active against any strains of MTb. Moreover, according to DFT calculations the formation of the acyl radical, a proposed intermediate in the INH oxidation, is favored in the [Ru(NH3)5(INH)](2+) complex by 50.7kcalmol(-1) with respect to the free INH. This result suggests that the stabilization of the acyl radical promoted by the metal center would be a more important feature than the oxidation potential of the INH for the antituberculosis activity against resistant strains.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Rutênio / Isoniazida / Mycobacterium tuberculosis / Antituberculosos Limite: Animals Idioma: En Revista: Eur J Pharm Sci Assunto da revista: FARMACIA / FARMACOLOGIA / QUIMICA Ano de publicação: 2015 Tipo de documento: Article País de afiliação: Brasil País de publicação: Holanda
Texto completo
Adicionar na Minha BVS
Imprimir
XML
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Rutênio / Isoniazida / Mycobacterium tuberculosis / Antituberculosos Limite: Animals Idioma: En Revista: Eur J Pharm Sci Assunto da revista: FARMACIA / FARMACOLOGIA / QUIMICA Ano de publicação: 2015 Tipo de documento: Article País de afiliação: Brasil País de publicação: Holanda