Table 1. Effect of phenyl derivatives and analogues of compound 01 upon the catalytic rate of S. pyogenes P5C reductase.
| Compound | Enzyme inhibition at 0.2 mMa | IC50 (μM)b |
|---|---|---|
| 01 | 3.0 ± 2.1 | ND |
| 02 | 8.1 ± 1.5 | ND |
| 03 | 3.0 ± 0.4 | ND |
| 04 | 3.0 ± 2.2 | ND |
| 05 | 33.4 ± 1.5 | >1 mM |
| 06 | 21.6 ± 1.5 | >1 mM |
| 07 | 3.2 ± 0.3 | ND |
| 08 | 91.1 ± 0.3 | 0.22 ± 0.02 |
| 09 | 70.5 ± 6.0 | 25.6 ± 9.6 |
| 10 | 98.4 ± 0.1 | 0.22 ± 0.01 |
| 11 | 95.4 ± 1.3 | 0.87 ± 0.10 |
| 12 | 52.0 ± 1.2 | 12.0 ± 6.1 |
| 13 | 63.9 ± 2.2 | 2.7 ± 0.8 |
| 14 | 96.2 ± 0.1 | 0.88 ± 0.07 |
| 15 | 92.5 ± 0.5 | 0.39 ± 0.02 |
| 16 | 61.5 ± 1.1 | 1.4 ± 0.3 |
| 17 | 71.2 ± 1.0 | 0.78 ± 0.09 |
| 18 | 71.2 ± 2.1 | 0.90 ± 0.13 |
| 19 | 94.5 ± 0.1 | 0.41 ± 0.05 |
| 20 | 33.8 ± 0.7 | >1 mM |
| 21 | 11.5 ± 3.9 | ND |
a
P5C-dependent NADH oxidation was measured at 37°C for 5 min in the presence of 0.2 mM of a given compound. Results were expressed as percent of the activity measured in parallel, untreated controls. At least three replications were run for each phosphonate, and six for the control. Data are presented as percent inhibition, and are means ± SE over replications
b
Active compounds (percent inhibition at 0.2 mM > 20%) were further tested in the micromolar range, from 0.1 to 100 μM. The concentrations causing 50% inhibition (IC50) were estimated utilizing the linear regression equation of enzyme activity values, expressed as a percentage of untreated controls, plotted against the logarithm of inhibitor concentration. ND not determined