title: IQG-607 abrogates the synthesis of mycolic acids and displays intracellular activity against Mycobacterium tuberculosis in infected macrophages.
abstract: In this work, the antitubercular activity of a pentacyano(isoniazid)ferrate(II) compound (IQG-607) was investigated using a macrophage model of Mycobacterium tuberculosis infection. Importantly, treatment of M.-tuberculosis-infected macrophages with IQG-607 significantly diminished the number of CFU compared with the untreated control group. The antitubercular activity of IQG-607 was similar to that observed for the positive control drugs isoniazid and rifampicin. Nevertheless, higher concentrations of IQG-607 produced a significantly greater reduction in bacterial load compared with the same concentrations of isoniazid. Analysis of the mechanism of action of IQG-607 revealed that the biosynthesis of mycolic acids was blocked. The promising activity of IQG-607 in infected macrophages and the experimental determination of its mechanism of action may help in further studies aimed at the development of a new antimycobacterial agent.
authors.affiliation: Centro de Pesquisas em Biologia Molecular e Funcional (CPBMF) and Instituto Nacional de Ciência e Tecnologia em Tuberculose (INCT-TB), Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, RS, Brazil; Programa de Pós-Graduação em Biologia Celular e Molecular, PUCRS, Porto Alegre, RS, Brazil; Programa de Pós-Graduação em Medicina e Ciências da Saúde, PUCRS, Porto Alegre, RS, Brazil.
authors.forename: Valnês S
authors.initials: VS
authors.lastname: Rodrigues-Junior
authors.affiliation: Centro de Pesquisas em Biologia Molecular e Funcional (CPBMF) and Instituto Nacional de Ciência e Tecnologia em Tuberculose (INCT-TB), Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, RS, Brazil; Programa de Pós-Graduação em Biologia Celular e Molecular, PUCRS, Porto Alegre, RS, Brazil.
authors.forename: André A
authors.initials: AA
authors.lastname: dos Santos Junior
authors.affiliation: Centro de Pesquisas em Biologia Molecular e Funcional (CPBMF) and Instituto Nacional de Ciência e Tecnologia em Tuberculose (INCT-TB), Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, RS, Brazil; Programa de Pós-Graduação em Biologia Celular e Molecular, PUCRS, Porto Alegre, RS, Brazil.
authors.forename: Anne D
authors.initials: AD
authors.lastname: Villela
authors.affiliation: Cátedra de Microbiología, Facultad de Ciencias Médicas, Universidad Nacional de Rosario, Rosario, Argentina.
authors.forename: Juan M
authors.initials: JM
authors.lastname: Belardinelli
authors.affiliation: Cátedra de Microbiología, Facultad de Ciencias Médicas, Universidad Nacional de Rosario, Rosario, Argentina.
authors.forename: Héctor R
authors.initials: HR
authors.lastname: Morbidoni
authors.affiliation: Centro de Pesquisas em Biologia Molecular e Funcional (CPBMF) and Instituto Nacional de Ciência e Tecnologia em Tuberculose (INCT-TB), Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, RS, Brazil; Programa de Pós-Graduação em Biologia Celular e Molecular, PUCRS, Porto Alegre, RS, Brazil; Programa de Pós-Graduação em Medicina e Ciências da Saúde, PUCRS, Porto Alegre, RS, Brazil.
authors.forename: Luiz A
authors.initials: LA
authors.lastname: Basso
authors.affiliation: Centro de Pesquisas em Biologia Molecular e Funcional (CPBMF) and Instituto Nacional de Ciência e Tecnologia em Tuberculose (INCT-TB), Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, RS, Brazil; Programa de Pós-Graduação em Medicina e Ciências da Saúde, PUCRS, Porto Alegre, RS, Brazil; Instituto de Toxicologia e Farmacologia, PUCRS, Porto Alegre, RS, Brazil. Electronic address: camposmmartha@yahoo.com.
authors.forename: Maria M
authors.initials: MM
authors.lastname: Campos
authors.affiliation: Centro de Pesquisas em Biologia Molecular e Funcional (CPBMF) and Instituto Nacional de Ciência e Tecnologia em Tuberculose (INCT-TB), Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, RS, Brazil; Programa de Pós-Graduação em Biologia Celular e Molecular, PUCRS, Porto Alegre, RS, Brazil. Electronic address: diogenes@pucrs.br.
authors.forename: Diógenes S
authors.initials: DS
authors.lastname: Santos
mesh_terms: D000995:Antitubercular Agents / Q000494:pharmacology*; D015169:Colony Count, Microbial; D005296:Ferrous Compounds / Q000494:pharmacology*; D006801:Humans; D007538:Isoniazid / Q000031:analogs & derivatives* / Q000494:pharmacology; D008264:Macrophages / Q000382:microbiology*; D050296:Microbial Viability / Q000187:drug effects; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000378:metabolism*; D009171:Mycolic Acids / Q000037:antagonists & inhibitors* / Q000378:metabolism*
chemical_list: D000995:Antitubercular Agents; D005296:Ferrous Compounds; D009171:Mycolic Acids; C576457:pentacyano(isoniazid)ferrate(II); D007538:Isoniazid
keywords: Drug development; IQG-607; Mycolic acid biosynthesis inhibitor; Tuberculosis