TABLE 4.
DHFR enzyme inhibition data
| Compound | IC50 (nM)a
|
% Human DHFR activityb | ||
|---|---|---|---|---|
| Wild-type DfrB (Tmps) | DfrB F98Y (Tmpr) | DfrA (S1) (Tmpr) | ||
| (RS)-BAL0030543 | 5.2 | 22.6 | 121.1 | 46.0 |
| (R)-BAL0031117 | 3.9 | 13.5 | 98.3 | 40.5 |
| (S)-BAL0031118 | 12.5 | 1146 | 1327 | 66.5 |
| (RS)-BAL0030544 | 11.3 | 70.2 | ND | ND |
| (R)-BAL0031115 | 9.2 | 40.9 | 35.1 | 68.7 |
| (S)-BAL0031116 | 37.6 | 2917 | 1009 | 88.5 |
| (RS)-BAL0030545 | 12.2 | 124.4 | 153.6 | 75.9 |
| (R)-BAL0031113 | 8.9 | 64.4 | 98.0 | 75.6 |
| (S)-BAL0031114 | 46.8 | 5705 | 2586 | 93.4 |
| Tmp | 25.7 | 10243 | 32997 | 74.0 |
a
IC50s were determined for S. aureus enzymes. ND, not done.
b
The activity of the human DHFR enzyme was determined in the presence of a 52 μM concentration of compound.