Table 1.
Enzyme Inhibition and In Vitro Antibacterial Activity of the ftuFabI Inhibitors
| Inhibition Constants and Mode of Inhibition | |||||
|---|---|---|---|---|---|
| Compound | MIC90 (μg/ml) | K1 (nM)a | K2 (nM)b | Type of Inhibition | |
|
1 | 0.000015 ± 0 | 0.051 ± 0.003 | 5 ± 35 μM | Slow-onset |
|
2 | 2.5 ± 0.2 | 2260 ± 107d | Rapid equilibrium | |
|
3 | 0.32 ± 0.02 | 289 ± 11d | Rapid equilibrium | |
|
4 | 0.001 ± 0.001 | 1.9 ± 0.1 | 308 ± 6 | Slow-onset |
|
5 | 0.004 ± 0.001 | 7.1 ± 0.2 | 149 ± 2 | Slow-onset |
|
6 | 0.21 ± 0.05 | 789 ± 13d | Rapid equilibrium | |
|
7 | 0.16 ± 0.07 | 1.9 ± 0.1 | 247 ± 5 | Slow-onset |
|
8 | 0.03 ± 0.001 | 2.1 ± 0.1 | 311 ± 20 | Slow-onset |
|
9 | 0.00018 ± 0.00014 | 0.44 ± 0.02 | 696 ± 70 | Slow-onset |
|
10 | 0.0012 ± 0.0002 | 1.3 ± 0.1 | 525 ± 8 | Slow-onset |
|
11 | 0.16 ± 0.06 | 2.7 ± 0.1 | 331 ± 6 | Slow-onset |
|
12 | 0.66 ± 0.14 | 23.6 ± 1.2 | 192 ± 2 | Slow-onset |
| Gentamicin | 4 | ND | ND | ND | |
| Streptomycin | 2 | ND | ND | ND | |
| Doxycycline | 0.75 ± 0.35 | ND | ND | ND | |
a
K1 refers to inhibition constant binding to E-NAD+.
b
K2 refers to inhibition constant binding to E-NADH.
c
K2 value obtained by varying the concentration of NADH.
d
Kis values for rapid, reversible inhibitors. ND, not determined.