TABLE 2.
Validated inhibitors from the LOPAC chemical library for Mycobacterium smegmatis grown under nutrient-rich and nutrient-limited culture conditionsa
| LOPAC compound | MIC (μM)b,c |
IC50 (μM) (mean ± SEM)b |
||||
|---|---|---|---|---|---|---|
| LB | C− | N− | LB | C− | N− | |
| BAY 11-7085 | 50 | 6.25 | 12.5 | 30.60 ± 0.59 | 2.58 ± 0.48 | 6.22 ± 0.11 |
| Calcimycin | 3.125 | 12.5 | 12.5 | 1.04 ± 0.24 | 5.21 ± 0.16 | 3.43 ± 0.19 |
| Calmidazolium chloride | 12.5 | 50 | 12.5 | 13.20 ± 1.17 | 13.85 ± 0.22 | 7.02 ± 1.51 |
| Carboplatin | 50 | 25 | 50 | 14.07 ± 4.27 | 12.14 ± 0.67 | 7.41 ± 0.25 |
| 4-Chloromercuribenzoic acid | 25 | 6.25 | 12.5 | 7.07 ± 0.75 | 7.65 ± 0.17 | 6.33 ± 0.11 |
| Cisplatin | >50 | 12.5 | 12.5 | >50 | 8.02 ± 3.44 | 10.31 ± 5.45 |
| Clotrimazole | 12.5 | 50 | 50 | 6.54 ± 0.77 | 18.21 ± 3.24 | 12.19 ± 0.07 |
| Demeclocycline | 3.125 | 6.25 | 6.25 | 1.88 ± 0.24 | 5.92 ± 0.28 | 4.40 ± 0.25 |
| Dequalinium analog C-14 | 6.25 | 6.25 | 3.125 | 3.95 ± 0.55 | 2.73 ± 0.40 | 1.74 ± 0.30 |
| Diphenyleneiodonium | 6.25 | 3.125 | 3.125 | 6.77 ± 0.43 | 8.53 ± 1.81 | 1.63 ± 0.30 |
| Doxycycline | 1.56 | 3.125 | 3.125 | 0.76 ± 0.05 | 2.98 ± 0.16 | 1.95 ± 0.57 |
| Idarubicin | 12.5 | 25 | 12.5 | 3.61 ± 2.01 | 6.68 ± 6.53 | 5.13 ± 0.23 |
| Lomefloxacin | 12.5 | 6.25 | 6.25 | 4.33 ± 0.10 | 4.88 ± 0.25 | 1.44 ± 0.15 |
| LY-367265 | 50 | 25 | 50 | 25.11 ± 6.96 | 25.26 ± 1.44 | 22.31 ± 0.34 |
| Methoctramine | 12.5 | 12.5 | 12.5 | 15.90 ± 1.98 | 6.88 ± 1.22 | 7.45 ± 0.40 |
| Minocycline | 12.5 | 12.5 | 12.5 | 6.77 ± 1.12 | 5.02 ± 1.15 | 7.23 ± 0.13 |
| Mitoxantrone | 50 | 50 | 50 | 21.84 ± 5.27 | 9.70 ± 0.84 | 5.02 ± 0.25 |
| Niclosamide | 12.5 | 6.25 | 6.25 | 6.85 ± 0.72 | 3.31 ± 1.21 | 4.73 ± 0.26 |
| Ofloxacin | 3.125 | 6.25 | 6.25 | 2.03 ± 0.65 | 3.13 ± 1.55 | 1.73 ± 0.37 |
| Pentamidine | 50 | 25 | 50 | 23.53 ± 0.15 | 11.05 ± 0.17 | 9.10 ± 0.26 |
| 1,10-Phenanthroline | 50 | 12.5 | 12.5 | 41.64 ± 0.31 | 4.99 ± 0.28 | 5.76 ± 0.32 |
| Se-methylselenocysteine | >50 | 12.5 | 12.5 | >50 | 2.19 ± 0.18 | 0.60 ± 0.09 |
| Ruthenium red | >50 | 50 | 50 | >50 | 17.71 ± 0.19 | 9.47 ± 0.11 |
| Trifluoperazine | 50 | 50 | 50 | 12.26 ± 0.06 | 12.35 ± 0.18 | 3.15 ± 1.04 |
| U-83836 | 50 | 50 | 50 | >50 | >50 | 34.25 ± 0.38 |
| Vancomycin | 12.5 | 25 | 25 | 3.18 ± 0.43 | 16.69 ± 0.19 | 11.12 ± 0.17 |
| WB64 | 50 | 50 | 25 | 8.15 ± 1.37 | 11.70 ± 5.73 | 6.00 ± 0.12 |
a
MIC and IC50s for M. smegmatis were determined using OD and/or fluorescence measurements for compounds that were detected as inhibitory in the LOPAC library screens. Validation of the hits was carried out using a starting concentration of 50 μM, and compounds were tested against M. smegmatis grown under nutrient-rich, carbon-limited, and nitrogen-limited culture conditions.
b
The mycobacteria were grown under nutrient-rich (LB) and carbon-limited (C−) and nitrogen-limited (N−) culture conditions.
c
Underlined MIC values indicate the growth condition under which an inhibitor was detected in screening.