Table 2.
Inhibitory activity against Streptococcus mutans dihydrofolate reductase (SmDHFR) and human DHFR (hDHFR)
| Compound | SmDHFR | hDHFR | SI c | |||
|---|---|---|---|---|---|---|
|
| ||||||
| IC50 (nM) a | Ki (nM) b | IC50 (nM) a | Ki (nM) b | IC50 | Ki | |
| #66 | 8.7 ± 1.9 | 3.4 ± 0.7 | 1027.0 ± 137.8 | 91.7 ± 4.6 | 117.8 | 26.7 |
| #151 | 7.1 ± 0.9 | 3.0 ± 0.1 | 52.8 ± 6.9 | 5.5 ± 1.0 | 7.5 | 1.8 |
| #153 | 8.2 ± 1.4 | 3.6 ± 0.1 | 53.5 ± 6.8 | 4.9 ± 1.5 | 6.5 | 1.4 |
| TMQ | 2.2 ± 0.7 | 1.3 ± 0.4 | 6.87 ± 0.52 | 1.88 | 3.1 | 1.4 |
IC50, 50% inhibitory concentration; Ki, inhibitory constant; SI, selectivity index.
a
IC50 = Ci/(Vo/Vi−1), where Vo and Vi are the initial velocities in the absence and presence of inhibitor, respectively, and Ci is the concentration of inhibitor.
b
Ki calculation uses the Michaelis–Menten equation for competitive inhibition.
c
SI is defined as IC50(hDHFR)/IC50(SmDHFR) or Ki(hDHFR)/Ki (SmDHFR).