Figure 3
Effect of SapM inhibitors 1, 2 and 13 on Mtb H37Rv growth and intracellular burden. Efficacy of compounds at 1 and 40 µM on Mtb intracellular burden in THP-1 macrophages at 24 h (A) and 72 h (B) post infection. Fold change of Mtb burden was calculated from the average CFU/ml relative to the DMSO control. Statistical significance was evaluated by one-way ANOVA (Dunnett’s test) compared to DMSO control (****p < 0.0001). Error bars in (A,B) indicate ± SD of two and three independent experiments, respectively. (C) Effect of compounds at 40 µM on the acellular growth of Mtb in Middlebrook 7H9 broth monitored over 9 days using optical density (OD600). DMSO and the first-line antibiotic isoniazid (at 0.14 µg/ml) were used as negative and positive controls, respectively. Error bars indicate ± SD of triplicates. Statistical significance was evaluated by two-way ANOVA (Dunnett’s test) compared to DMSO control (****p < 0.0001). (D) THP-1 macrophage viability at 72 h upon treatment with compounds at 10 and 40 µM. Percentage of viability was calculated relative to the control (RPMI media only). Dashed black line indicates 70% viability. Error bars indicate ± SD of three independent experiments.
