Table 1.
Antibacterial and Potentiation Activity for Substituted Cinnamoyl Analogsi
| |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| MIC (μM)a |
potentiationb (μM) |
||||||||||
| # | R | WT | WT-pore | ΔtolC | ΔtolC-pore | MPC4 (NOV) | MPC4 (ERY) | CC50 (μM)c | WT/WTpored | WT-pore/ΔtolC-poree | efflux inhibition,f SS ratio 32 μM/0 μM |
| Ng | 128 | 32−64 | 0.5 | 0.125 | NA | NA | NA | NA | NA | NA | |
| Eh | 64 | 4−8 | 2 | 0.125 | NA | NA | NA | NA | NA | NA | |
| 2 | 2-Cl | 200 | 100 | 12.5 | 12.5 | 1.56 | 3.1 | 10.0 | 2 | 8 | 6.5 |
| 6 | 2-Br | 25 | 25 | 12.5 | 12.5 | 12.5 | 3.1 | 11.7 | 1 | 2 | 7.2 |
| 7 | 2-F | 100 | 100 | 50 | 50 | 12.5 | 12.5 | 28.3 | 1 | 2 | 3.9 |
| 8 | 2-Me | 50 | 25 | 25 | 50 | 6.25 | 12.5 | ND | 2 | 0.5 | 5.9 |
| 9 | 2-NO2 | >400 | >400 | >400 | >400 | >200 | >200 | ND | 1 | 1 | 1 |
| 10 | 3-Cl | 25 | 25 | 12.5 | 6.25 | 6.25 | 6.25 | 10.1 | 1 | 4 | 8.3 |
| 11 | 4-Cl | 25 | 12.5 | 12.5 | 6.25 | 6.25 | 6.25 | 11.2 | 2 | 2 | 11.2 |
| 12 | 4-Br | >200 | >200 | 25 | 12.5 | 200 | 200 | ND | 1 | >16 | 12.3 |
| 13 | 4-iPr | 50 | 25 | 25 | 25 | 12.5 | 12.5 | 13.3 | 2 | 1 | 5.5 |
| 14 | 2,3-diCl | >200 | 400 | 12.5 | 6.25 | 400 | 200 | ND | 1 | 64 | 1 |
MIC values, determined as the average of two replicates.
Minimum concentration of test compound required to reduce the MIC of novobiocin (NOV) or erythromycin (ERY) by 4-fold measured in WT-pore cells.
Measured in A549 cells; values are the average of two replicates.
The ratio of MIC values for compounds in WT cells vs permeated WT-pore cells.
The ratio of MIC values for compounds in WT-pore cells vs ΔtolC-pore cells.
Accumulation of Nile Red fluorescent probe in WT-pore cells in the presence (32 μM) and absence (0 μM) of each compound.
Values for novobiocin.
Values for erythromycin.
MIC = minimum inhibitory concentration; WT = wild-type; ND = not determined; SS = steady state; NA = not applicable.