Table 1.
In vitro antiviral activity and cytotoxicity of compounds 12a-b, 14a-b, 19a-b, 9a-b, 10a-b, 11a-b and phosphoramidate prodrug 24.a
| Cmpd | Janus Type | Anti-HCV activity (μM)
|
rRNA (μM)
|
Anti-HIV-1 activity (μM)
|
Cytotoxicity, CC50 (μM)
|
||||
|---|---|---|---|---|---|---|---|---|---|
| EC50 | EC90 | CC50b | EC50 | EC90 | PBM | CEM | Vero | ||
| 12a | J-AU | 5.7 | 9.4 | 5.7 | 6.8 | 16.5 | 51.8 | 7.9 | 13.4 |
| 12b | J-AU | > 10 | > 10 | > 10 | > 100 | > 100 | > 100 | >100 | > 100 |
| 14a | J-AA | > 10 | > 10 | > 10 | > 100 | > 100 | 53.8 | 29.5 | 82.5 |
| 14b | J-AA | > 10 | > 10 | > 10 | ≥100 | ≥100 | > 100 | >100 | > 100 |
| 19a | J-GA | 3 | 22.5 | < 10 | 9.4 | 24.0 | 3.1 | 20.2 | 63.1 |
| 19b | J-GA | ~ 3 | 17.9 | ~ 3 | 3.3 | > 100 | 92.1 | 36.5 | > 100 |
| 24 | NA | > 10 | >10 | >10 | ND | ND | ND | ND | ND |
| 9a | NA | > 10 | > 10 | > 10 | 2.7 | 16.2 | 10.5 | 65.1 | 87.3 |
| 9b | NA | > 10 | > 10 | > 10 | >100 | > 100 | > 100 | > 100 | > 100 |
| 10a | NA | 0.2 | 0.3 | 0.15 | 0.38 | 1.1 | 0.10 | ND | 0.96 |
| 10b | NA | 6.8 | 21.8 | ~ 10 | 24.7 | 56.0 | 4.9 | 10.0 | > 100 |
| 11a | NA | 0.5 | 2.4 | ~ 10 | 0.49 | 1.5 | 3.1 | <1.0 | 7.6 |
| 11b | NA | > 10 | > 10 | > 10 | > 100 | > 100 | > 100 | > 100 | > 100 |
| 16a | NA | > 10 | > 10 | > 10 | 9.6 | 30.2 | 2.9 | 8.2 | 43.1 |
| 16b | NA | > 10 | > 10 | > 10 | > 100 | > 100 | > 100 | > 100 | > 100 |
| AZT | NA | > 10 | > 10 | > 10 | 0.0040 | 0.028 | > 100 | 14.3 | 53.0 |
a
All values are based on mean of replicate assays (n ≥ 2)
b
CC50: cytotoxic concentration that reduced the rRNA levels by 50% at 120 h.
ND: not determined.