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 (250mg/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 250mg/kg. The activity of test compounds was compared with that of the positive control drug isoniazid (INH) (25mg/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.