Activity of IQG-607, a new orally active compound, in a murine model of Mycobacterium tuberculosis infection

[Fe(CN)5(isoniazid)]3−: An iron isoniazid complex with redox behavior implicated in tuberculosis therapy

“…Additionally, a semi-quantitative strip test for free cyanide did not show evidence of any significant cyanide release. These data are in agreement with the low toxicity described for other related cyanoferrate complexes and along with our own toxicological data for IQG607 in mice [22,41].…”

“…IQG607 has emerged as a promising anti-tuberculosis candidate, being effective against Mtb both in vitro and in a murine model [22]. This work has provided evidence of IQG607 stability including, upon oxidation, mediated by hydrogen peroxide.…”

“…IQG607 has shown anti-proliferative activity in Mtb-infected macrophage and Mtbinfected mouse model [22], and disrupts mycolic acid biosynthesis in isoniazidsensitive M. tuberculosis H37Rv strain [24].Accordingly, IQG607 appears to be a promising candidate for anti-tuberculosis therapy. However, there is still a lack of detailed studies of IQG607 stability in the presence of oxidizing agents and, particularly, its potential for generation of radicals, which might be of key importance in the proposed redox-mediated-activation mechanism.…”

Functional, thermodynamics, structural and biological studies of in silico-identified inhibitors of Mycobacterium tuberculosis enoyl-ACP(CoA) reductase enzyme

“…The macrophage murine cell line RAW 264.7 was cultured in DMEM (Gibco) supplemented with 10% heat inactivated fetal bovine serum (FBS) and 1% Penicillin-Streptomycin at 37 °C with 5% CO 2 . Macrophage infection procedures were performed essentially as described elsewhere24. Briefly, macrophages were seeded in 24-well culture plates at a density of 10 5 cells per well in DMEM medium (supplemented with 10% FBS) and incubated for 24 h at 37 °C with 5% CO 2 .…”

“…Infection of RAW 264.7 cells with M. tuberculosis H37Rv was performed at a multiplicity of infection of 1:1 (bacteria per macrophage) for 3 h at 37 °C with 5% CO 2 . Infected RAW 264.7 cells were washed three times with sterile 0.9% saline solution to remove extracellular bacteria and replaced with 1 mL fresh DMEM (supplemented with 10% FBS)24. A control group of infected macrophages without any previous treatment was lysed with 0.025% sodium dodecyl sulfate (SDS) dissolved in sterile 0.9% saline solution in the day of treatment onset; this group was named “early control”.…”