title: Activity of IQG-607, a new orally active compound, in a murine model of Mycobacterium tuberculosis infection.
abstract: We have previously demonstrated a potent in vitro inhibitory activity for two pentacyano(isoniazid)ferrate(II) compounds, namely IQG-607 and IQG-639, against the Mycobacterium tuberculosis enoyl-acyl carrier protein reductase enzyme. In this study, the activity of these compounds was evaluated using an in vivo murine model of tuberculosis. Swiss mice were infected with M. tuberculosis H37Rv strain and then IQG-607 or IQG-639 (250 mg/kg) was administered for 28 days or 56 days. In addition, a dose-response study was performed with IQG-607 at 5, 10, 25, 50, 100, 200 and 250 mg/kg. The activity of test compounds was compared with that of the positive control drug isoniazid (INH) (25 mg/kg). After 28 days or 56 days of treatment, both IQG-607 and INH significantly reduced M. tuberculosis-induced splenomegaly as well as significantly diminishing the colony-forming units in the spleen and lungs. IQG-607 and INH ameliorated the lung macroscopic aspect, reducing lung lesions to a similar extent. However, IQG-639 did not significantly modify any evaluated parameter. Experiments using early and late controls of infection revealed a bactericidal activity for IQG-607. IQG-607 might well represent a good candidate for clinical development as a new antimycobacterial agent.
authors: 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), Av. Ipiranga 6681 - Prédio 92A Tecnopuc, 90619-900 Porto Alegre, RS, Brazil.
authors: Valnês S
authors: VS
authors: Rodrigues-Junior
authors: André
authors: A
authors: Dos Santos Junior
authors: Anderson Jader
authors: AJ
authors: Dos Santos
authors: Cristopher Zandoná
authors: CZ
authors: Schneider
authors: João B
authors: JB
authors: Calixto
authors: Eduardo Henrique Silva
authors: EH
authors: Sousa
authors: Luiz Gonzaga
authors: LG
authors: de França Lopes
authors: André Arigony
authors: AA
authors: Souto
authors: Luiz Augusto
authors: LA
authors: Basso
authors: Diógenes Santiago
authors: DS
authors: Santos
authors: Maria M
authors: MM
authors: Campos
mesh_terms: D000818:Animals; D000995:Antitubercular Agents / Q000494:pharmacology*; D058491:Bacterial Load; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D005296:Ferrous Compounds / Q000494:pharmacology; D007538:Isoniazid / Q000031:analogs & derivatives / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects / Q000382:microbiology / Q000473:pathology; D008171:Lung Diseases / Q000188:drug therapy / Q000382:microbiology; D008297:Male; D051379:Mice; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000472:pathogenicity; D010069:Oxadiazoles / Q000494:pharmacology; D014376:Tuberculosis / Q000188:drug therapy* / Q000382:microbiology
chemical_list: D000995:Antitubercular Agents; D005296:Ferrous Compounds; D010069:Oxadiazoles; C576458:pentacyano(2-methyl-5-(pyridin-4-yl)-1,3,4-oxadiazole)ferrate(II); C576457:pentacyano(isoniazid)ferrate(II); C058614:pentacyanoferrate (II); D007538:Isoniazid