Table IV.
In vitro antiviral activity (EC50 and EC90), cytotoxicity (CC50) and their selectivity indices (SI) of prodrugs of ACV against HSV-1, HSV-2, HCMV and EBV.
EC50 = Compound concentration that reduces viral replication by 50%, in units of μM concentration.
EC90 = Compound concentration that reduces viral replication by 90%, in units of μM concentration.
CC50 = Compound concentration that reduces cell viability by 50%, in units of μM concentration.
SI50 = Selectivity index calculated as the CC50 divided by the EC50.
SI90 = Selectivity index calculated as the CC90 divided by the EC90.
| Drug/Prodrug | Herpes Simplex Virus-1 (HSV-1) | Herpes Simplex Virus-2 (HSV-2) | Human Cytomegalovirus (HC MV)* | Epstein-Barr Virus (EBV) | ||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
| ||||||||||||||||||||
| EC5o (μM) | EC90 (μM) | CC50 (μM) | SI50 (μM) | SI90 (μM) | EC50 (μM) | EC90 (μM) | CC50 (μM) | SI50 (μM) | SI90 (μM) | EC50 (μM) | EC90 (μM) | CC50 (μM) | SI50 (μM) | SI90 (μM) | EC50 (μM) | EC90 (μM) | CC50 (μM) | SI50 (μM) | SI90 (μM) | |
|
| ||||||||||||||||||||
| ACV/GCV* | 3.43 | >100 | >100 | >29.15 | 1 | 5.98 | >100 | >100 | >16.72 | 1 | 0.21 | 0.38 | >100 | >476.19 | >263.16 | 12.4 | 67.3 | >100 | >8.06 | >1.49 |
| B-ACV | 181.54 | >300 | >300 | >1.65 | 1 | >300 | >300 | >300 | 1 | 1 | >60 | >60 | 234.24 | <3.9 | <3.9 | 22.3 | 52.8 | >60 | >2.69 | >1.14 |
| R-ACV | 8.3 | 168.32 | >300 | >36.14 | >1.78 | 3.4 | 8.89 | >300 | >88.24 | >33.75 | 46.47 | >300 | >300 | >6.46 | 1 | 10.7 | 49.5 | >60 | >5.61 | >1.21 |
| B-R-ACV | 5.7 | 21.89 | >300 | >52.6 | >13.7 | 0.27 | 11.39 | >300 | >1111.11 | >26.34 | 70.07 | 99.96 | >300 | >4.28 | >3 | 2.1 | 41.5 | >60 | >28.57 | >1.45 |
| 12HS-ACV | 1.16 | 6.24 | 296.07 | 255.23 | 47.22 | 0.41 | >300 | 296.07 | 722.12 | 0.99 | 101.02 | 136.55 | >300 | >2.97 | >2.2 | 35.8 | 55 | 47.3 | 1.32 | 0.86 |
| B-12HS-ACV | <0.096 | 0.42 | >300 | >3125 | >714.29 | <0.096 | 4.65 | >300 | >3125 | >64.52 | >300 | >300 | >300 | 1 | 1 | 37.2 | >60 | >60 | >1.61 | 1 |