Table 4.
Inhibitory activity against viral and human DNA polymerases of thymine-α-CNP derivatives with a modified cyclic linker moiety.
| Compound | IC50a (μM)
|
|||||
|---|---|---|---|---|---|---|
| HIV-1 RT | HCMV DNA Pol | HSV-1 DNA Pol | VZV DNA Pol | Human DNA Pol α | Human DNA Pol β | |
| 6a | ≥500 | 40±25 | 14±14 | 73±1 | 165±100 | >500 |
| 6b | 440±85 | 4.6±0.2 | 36±12 | 12±3 | 183±8 | 390±127 |
| 6c | 425±106 | 3.0±0.5 | 14±3 | 8.5±2.1 | 48±36 | >500 |
| 6d | 131±86 | 13±4 | 7.5±5.0 | 2.9±0.7 | 75±18 | 76±30 |
| 6e | ≥500 | 4.0±0.0 | 8.6±6.6 | 16±1 | 69±21 | >500 |
| 6f | >500 | 38±6 | 25±21 | 24±4 | 332±28 | 361±160 |
|
| ||||||
| Thymine α-CNP | 0.40±0.05 | 38±11 | 26±20 | 38±16 | 229±27 | >500 |
| PFA | 0.34±0.01 | 9.8±5.8 | 0.44±0.25 | 0.18±0.01 | 7.7±6.5 | >100 |
| BVDU-TP | 0.89±0.4 | 3.6±0.7 | 1.9±0.9 | 0.49±0.09 | 21±10 | 26±4 |
a
IC50 or 50% inhibitory concentration.