FIG 3.

In vivo activity of compound 1, as shown in an acute monotherapy model (A) and a chronic combination therapy model (B, C). For the acute model, mice were infected with 3.2 log₁₀ CFU by the aerosol route and treatment was initiated on day 1 after infection. For the chronic model, mice were infected with 2.0 log₁₀ CFU by the aerosol route and treatment was initiated 28 days after infection. CFU in the lungs were determined after 4 weeks (A) or 8 weeks (B) of treatment. UT, untreated; E, ethambutol (100 mg/kg); RIF, rifampin (10 mg/kg); INH, isoniazid (10 mg/kg); 1_50, compound 1 at 50 mg/kg. All treatment was daily, 5 days a week. Data are shown as mean ± SD (*, P < 0.05; **, P < 0.01; ***, P < 0.001; ****, P < 0.0001 by one-way ANOVA and Tukey’s multiple-comparison test). (C) Bliss independence model demonstrated synergistic effects of the combination of 1 and rifampin and INH and rifampin (unpaired t test applied).