Table 2.
Inhibitory efficiencies of hydrazine analogs on MPO activity, as measured in the MPO fluorescence stopped flow assay and simultaneous fit with either a 1 or 2-step slow tight-binding mechanism using DynaFit 3. Fixed constants k+1 = 10 μM−1s−1, k−1 = 80 s−1, k+2 = 224 s−1.
| Inhibitors | k+3 (μM−1s−1) | k−3 (s−1) | k+4 (s−1) | k−4 (s−1) | Ki (μM) | Ki* (μM) |
|---|---|---|---|---|---|---|
| 2-ABAH | 0.10 ± 0.0014 | 0.026 ± 0.0003 | 0.0067 ± 0.0004 | 0.0094 ± 0.002 | 0.26 | 0.16 |
| 4-ABAH | 0.13 ± 0.0007 | 0.031 ± 0.0001 | 0.038 ± 0.003 | 0.73 ± 0.06 | 0.24 | 0.23 |
| 3-DMABAH | 0.09 ± 0.0009 | 0.05 ± 0.0005 | - | - | 0.56 | - |
| BAH | 0.0098 ± 5.47E-05 | 0.0068 ± 9.5E-05 | - | - | 0.69 | - |
| 4-FBAH | 0.0075 ± 4.93E-05 | 0.0062 ± 0.0001 | - | - | 0.83 | - |
| NaN3 | 0.185 ± 0.0018 | 0.156 ± 0.001 | - | - | 0.84 | - |
| 4-TFMBAH | 0.0013 ± 1.36E-05 | 0.004 ± 0.0002 | - | - | 3.08 | - |
| 4-NBAH | 0.0027 ± 1.65E-05 | 0.01 ± 0.0001 | - | - | 3.70 | - |
| Isoniazid | 0.0011 ± 7.31E-06 | 0.011 ± 0.0001 | - | - | 10.00 | - |