Table 1.
Inhibitory effects of ANPs on the replication of human gammaherpesviruses
| Compound | KSHV |
EBV |
||||||
|---|---|---|---|---|---|---|---|---|
| Antiviral activity (μM)a |
CC50 (μM)b | SIc | Antiviral activity (μM)a |
CC50 (μM)b | SIc | |||
| EC50 | EC90 | EC50 | EC90 | |||||
| HPMPC | 1.3 ± 0.29 | 2.2 ± 1.3 | 609 ± 92 | 468 | 1.9 ± 1.6 | 20 ± 1.6 | >500 | >263 |
| Cyclic HPMPC | 2.4 ± 1.0 | 3.7 ± 3.7 | 589 ± 121 | 245 | 41 ± 24 | 256 ± 286 | >500 | >15 |
| HDP-HPMPC | 0.7 ± 0.1 | 59 ± 18 | >125 | >179 | 0.3 ± 0.2 | 5.2 ± 5.9 | >125 | >417 |
| HPMP-5-azaC | 0.7 ± 0.4 | 9.6 ± 7.1 | >500 | >714 | 3.2 ± 1.8 | 50 ± 40 | >500 | >156 |
| Cyclic HPMP-5-azaC | 3.1 ± 0.8 | 4.6 ± 11 | 462 ± 31 | 149 | 1.1 ± 0.2 | 7.6 ± 9.2 | >500 | >455 |
| HPMPA | 0.7 ± 0.7 | ≥96 | 406 ± 3 | 580 | 3.6 ± 5.3 | 36 ± 36 | >500 | >139 |
| Cyclic HPMPA | 0.7 ± 0.4 | ≥112 | 428 ± 189 | 611 | 39 ± 25 | 312 ± 217 | >500 | >13 |
| 3-Deaza-HPMPA | 0.3 ± 0.2 | 3.0 ± 1.7 | 97 ± 46 | 323 | 0.7 ± 0.7 | 28 ± 22 | >500 | >714 |
| Cyclic 3-deaza-HPMPA | 1.8 ± 0.4 | 3.9 ± 3.2 | 84 ± 70 | 47 | 39 ± 9 | 496 ± 127 | >500 | >139 |
| 7-Deaza-HPMPA | 5.0 ± 0.3 | 12 ± 6.6 | 30 ± 10 | 6 | 5.3 ± 9.3 | 66 ± 0 | ≥470 | 89 |
| Cyclic 7-deaza-HPMPA | 1.4 ± 5.6 | 2.5 ± 0.4 | 116 ± 25 | 83 | ≥239 | >500 | >500 | 2 |
| HPMPDAP | 0.9 ± 0.3 | 31 ± 22 | 459 ± 157 | 510 | 38 ± 28 | ≥336 | >500 | >13 |
| Cyclic HPMPDAP | 2.0 ± 1.3 | 7.3 ± 6.7 | 107 ± 47 | 54 | >500 | >500 | >500 | 1.0 |
| HPMPO-DAPy | 5.1 ± 1.4 | 17 ± 0 | 139 ± 129 | 27 | 59 ± 24 | >500 | >500 | >8 |
| Cyclic HPMPO-DAPy | 111 ± 20 | > 500 | 627 ± 211 | 6 | >500 | >500 | >500 | 1.0 |
| PMEA | 44 ± 15 | ≥172 | 44 ± 26 | 1 | 13 ± 3.3 | 55 ± 29 | >500 | >38 |
| PMEDAP | 16 ± 7.6 | >174 | 14 ± 7 | 1 | 7.6 ± 4.2 | 90 ± 73 | >500 | >66 |
| PMEO-DAPy | 12 ± 5.0 | ≥159 | 27 ± 11 | 2 | 5.0 ± 2.3 | 23 ± 3.8 | >500 | >100 |
a
The concentrations required to reduce KSHV or EBV DNA synthesis in TPA-stimulated BCBL-1 or P3HR-1 cells by 50 or 90%. Means ± standard deviations are shown where applicable.
b
The concentration required to reduce the growth of uninduced BCBL-1 or P3HR-1 cells by 50%. Means ± standard deviations are shown where applicable.
c
The selectivity index (ratio of the CC50 to the EC50).