2. Compound Activity against M. tuberculosis MmpL3 Mutant Strains .
| WT |
MmpL3F255L,V646M,F644I
|
MmpL3S591I
|
||||
|---|---|---|---|---|---|---|
| Series | Compound | IC90 (μM) | IC90 (μM) | Fold change | IC90 (μM) | Fold change |
| 7-aza | 1 | 0.061 | >100 | >1639 | - | - |
| 2 | 0.14 | >13 | >93 | - | - | |
| 3 | 0.17 | >50 | >294 | - | - | |
| DDU01 | 4 | 2.0 | >20 | >10 | - | - |
| 5 | 5.5 | >100 | >18 | - | - | |
| 6 | 0.19 | >100 | >526 | - | - | |
| ICA | 7 | 0.024 | 1.3 | 54 | - | - |
| 8 | 0.029 | >2.5 | >86 | - | - | |
| 9 | 0.071 | >5.0 | >70 | - | - | |
| DDU02 | 10 | 32 | >100 | >3 | - | - |
| 11 | 8.6 | >100 | >11 | - | - | |
| 12 | 13 | >95 | >7 | - | - | |
| DDU03 | 13 | 11 | >20 | >1.8 | - | - |
| 14 | 8.3 | >100 | >12 | - | - | |
| 15 | 20 | >100 | >5 | - | - | |
| DDU04 | 16 | 12 | >20 | >1.7 | - | - |
| 17 | 3.0 | >20 | >6.7 | - | - | |
| 18 | 15 | >100 | >6.7 | - | - | |
| DDU05 | 19 | 8.9 | 9.6 | 1.1 | - | - |
| 20 | 6.1 | 2.3 | 0.38 | - | - | |
| 21 | 4.8 | 7.1 | 1.5 | - | - | |
| Oxazole | 22 | 0.48 | 13 | 27 | - | - |
| 23 | 0.078 | 5.1 | 65 | - | - | |
| 24 | 0.62 | >100 | >161 | - | - | |
| Pyrazole | 25 | 0.27 | 0.64 | 2.4 | - | - |
| 26 | 2.3 | 2.2 | 0.96 | 52 | 23 | |
| ARI | 27 | 0.58 | 9.5 | 16 | - | - |
| 28 | 1.1 | >20 | >18 | - | - | |
| 29 | 2.3 | 12 | 5.2 | - | - | |
| Thiazole | 30 | 0.18 | 0.92 | 5.1 | - | - |
| 31 | 0.19 | >100 | >526 | - | - | |
| 32 | 0.088 | 3.0 | 34 | - | - | |
| AU1235 | - | 0.22 | >100 | 454 | 6.0 | 27 |
a
Inhibition of growth was measured after 5 days exposure to the compound. IC90 values show the geometric mean of at least two independent experiments to 2 s.f.. Fold change was calculated relative to WT IC90.