Table 1. Kinetic Evaluation of 1–3 Reveals Species Selectivitya.
| IC50 (nM) |
Ki (nM)b |
||||
|---|---|---|---|---|---|
| compd | tgTS | hTS | tgTS | hTS | selectivity (hTS Ki/tgTS Ki) |
| 1 | 21 ± 13 | 28.8 ± 21 | 1.8 ± 1.1 | 3.3 ± 2.4 | 1.83 |
| 2 | 23 ± 6.6 | 481 ± 162 | 2.0 ± 0.6 | 55.7 ± 18.8 | 27.9 |
| 3 | 35.8 ± 2.9 | 3250 ± 184 | 3.1 ± 0.25 | 378 ± 21 | 121.9 |
a
T. gondii TS-DHFR (25 nM) and human TS (50 nM) were preincubated with 100 μM dUMP and inhibitor. The reaction was initiated with 100 μM methyleneTHF.
b
Because of the concentrations of enzyme required for assay and the limits of detection, for those compounds having Ki values in the lower nanomolar range, the values reported represent an upper limit.