Table 1:
Biochemical and antibacterial activity of the monovalent inhibitors
| Compound | IC50 (nM)a | MIC (μM)b | |||||
|---|---|---|---|---|---|---|---|
| WTc | WTc + PMBNf |
ΔacrABd | ΔacrABd + PMBNf |
ΔtolCe | ΔtolCe + PMBNf |
||
| 1 | ≤ 1 | ≥ 25 | 3.13 | 3.13 | 0.78 | 1.56 | 0.78 |
| 3 | 4.5 ± 1.8 | > 25 | 3.13 | 25 | 0.39 | 1.56 | 0.1 |
| 9a | ≤ 1 | > 25 | 12.5 | > 25 | 0.78 | 1.56 | 0.78 |
| 9b | 19 ± 4 | > 25 | > 25 | > 25 | 3.13 | 3.125 | 1.56 |
| 9c | 32 ± 6 | > 25 | > 25 | > 25 | 6.25 | 6.25 | 6.25 |
| 9c-p | 849 ± 166 | NDg | NDg | >25 | >25 | >25 | >25 |
| 9d | 98 ± 21 | > 25 | > 25 | > 25 | 25 | 25 | 12.5 |
| 9e | 82 ± 17 | > 25 | > 25 | > 25 | > 25 | 25 | 12.5 |
| 9f | 64 ± 11 | > 25 | > 25 | > 25 | > 25 | 25 | 12.5 |
| 9g | 126 ± 36 | > 25 | > 25 | > 25 | > 25 | > 25 | 12.5 |
| 14 | 74 ± 12 | > 25 | 12.5 | > 25 | 1.56 | 1.56 | 0.2 |
a
ACC activity was determined using a fluorescence polarization assay. Reactions were performed in triplicate and the errors are standard deviation from the mean.
b
MIC values were determined by the microbroth dilution method. Experiments were performed in triplicate.
c
Wild-type, E. coli strain (K-12, MG1655).
d
E. coli ΔacrAB, knockout of the acrAB inner efflux pump.
e
E. coli ΔtolC, knockout of the tolC outer efflux pump.
f
PMBN was present at final concentration of 6 μM (8 μg/mL).
g
ND, not determined.