FIG 1.

(A) Chemical structures of a few of the primary hits (therapeutic index [Ti] > 21) identified in this study. (B) Antimycobacterial activity of identified hits in liquid cultures. For in vitro killing experiments, M. bovis BCG was grown until the OD₆₀₀ was 0.2 and subsequently exposed to the drugs at 8× MIC. After 7 days of incubation, bacterial counts were enumerated by plating 100 μl of 10-fold serial dilutions on MB 7H11 plates at 37°C for 3 to 4 weeks. The data presented in this panel are means ± SEs for duplicate samples and are representative of those from three independent experiments. Significant differences were observed for the indicated groups and were determined by a paired (two-tailed) t test. *, P < 0.05; **, P < 0.01. (C and D) Antimycobacterial activity of the identified hits in macrophages. THP-1 macrophages were seeded at a density of 2 × 10⁵ and infected with either M. bovis BCG (C) or M. tuberculosis (D) at an MOI of 1:10. At 24 h postinfection, the macrophages were washed and overlaid with RPMI medium containing the various drugs (8× MIC) for 4 days. For bacterial enumeration, macrophages were lysed in 1 ml of 1× PBS–0.1% Triton X-100, and 100 ml of 10-fold serial dilutions was plated on MB 7H11 plates at 37°C for 3 to 4 weeks. The data shown in this panel are means ± SEs for triplicate wells and are representative of those from three independent experiments. Significant differences were observed for the indicated groups and were determined by a paired (two-tailed) t test. *, P < 0.05; **, P < 0.01. UT, untreated.