Table 1.
Antiviral and cytotoxic/static activity of the compounds against herpesviruses and poxviruses in cell culture.
| Compounds | Antiviral activity: EC50 (μM) in HEL (human embryonic lung) fibroblasts except for feline herpesvirus and selectivity indexes (in bold italics) |
Cytotoxicity in HEL cells (μM) |
|||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| VZV |
HSV-1 |
HSV-2 |
HSV-1 TK– |
Cytomegalovirus |
Feline herpesvirusa | Vaccinia virus |
Cell morphology |
Cell growth |
|||||
| TK+ strains |
TK− strains |
||||||||||||
| YS | Oka | 07/01. | YS/R | KOS | G | KOS ACVr | AD-169 | Davis | Lederle | MCC | CC50 | ||
| 3 | N.D. | >23.4 | >23.4 | N.D. | >117 | >117 | >117 | >23.4 | >23.4 | >23.4 | >117 | ≥117 | 117 |
| 4 | N.D. | >23 | >23 | N.D. | >115 | >115 | >115 | >23 | >23 | >115 | >115 | ≥23 | >115 |
| 5 | N.D. | >35 | >35 | N.D. | >35 | >35 | >35 | >35 | >35 | >35 | >35 | 175 | 78 |
| 6 | 0.19 | 0.14 ± 0.04 | 0.30 ± 0.13 | N.D. | 1.37 ± 0 | 1.9 ± 0.7 | 2.8 ± 0.4 | 0.13 ± 0.05 | 0.06 ± 0.01 | >171 | ≥34 | ≥34 | 26 ± 12 |
| 137 | 186 | 87 | 19 | 14 | 9 | 200 | 433 | <1 | |||||
| 13 | N.D. | >23 | >4.6 | N.D. | >115 | >115 | >115 | >23 | >23 | >115 | >115 | ≥23 | >115 |
| 14 | 1.2 ± 0.4 | 3.9 ± 1.9 | 1.4 ± 0.7 | 2.0 ± 2.4 | 11.9 ± 2.4 | 23.2 ± 21.6 | 30.5 ± 11.2 | 11.9 | 10.1 | >113 | 44.7 ± 8.8 | ≥22.6 | >113 |
| >94 | >29 | >81 | >57 | >9 | >5 | >4 | >9 | >11 | >2.5 | ||||
| 15 | N.D. | >6.8 | 4-Aug | N.D. | >6.8 | >6.8 | >6.8 | >34 | 15.2 | >34 | >6.8 | ≥34 | 66 ± 46 |
| 16 | 0.0025 | 0.002 | 0.0017 | N.D. | 0.008 ± 0.004 | 0.007 ± 0.002 | 0.012 ± 0.007 | 0.0066 | 0.0022 | >1.33 | 0.011 ± 0.001 | ≥1.3 | 0.72 ± 0.27 |
| 288 | 360 | 423 | 90 | 103 | 60 | 109 | 327 | 65 | |||||
| 17 | N.D. | >1.4 | >1.4 | N.D. | >7 | >7 | >7 | >7 | >7 | >176 | >7 | ≥7 | >176 |
| 18 | 0.001 ± 0.001 | 0.007 ± 0.010 | 0.005 ± 0.007 | 0.005 ± 0.007 | 0.034 ± 0 | 0.08 ± 0.08 | 0.09 ± 0.02 | 0.005 ± 0.005 | 0.002 ± 0.002 | 0.43 ± 0.36 | 0.13 ± 0.06 | ≥171.3 | 19 ± 14 |
| 19,000 | 2700 | 3800 | 3800 | 559 | 238 | 211 | 3800 | 9500 | 398 | 146 | |||
| (S)-HPMPG | N.D. | 0.56 ± 0.13 | 0.21 ± 0.15 | N.D. | 0.78 ± 0.22 | 0.78 ± 0.22 | 0.78 ± 0.22 | 1.8 ± 1.1 | 1.5 ± 0.6 | 0.72 ± 0.50 | 1.1 ± 0.22 | >100 | 39 ± 7 |
| 70 | 186 | 50 | 50 | 50 | 22 | 26 | 157 | 35 | |||||
| (S)-cHPMPG | N.D. | 0.1 ± 0.1 | 0.23 ± 0.10 | N.D. | 0.66 ± 0.47 | 0.66 ± 0 | 0.50 ± 0.23 | 1.5 ± 0 | 1.6 ± 0 | 0.90 ± 0.40 | 1.0 ± 0.5 | >100 | 17 ± 10 |
| 170 | 74 | 26 | 26 | 34 | 11 | 11 | 96 | 17 | |||||
| Brivudin | 0.006 ± 0.004 | 0.01 ± 0.01 | 53 ± 67 | ≥120 ± 42 | 0.038 ± 0.034 | 105 ± 32 | ≥183 ± 103 | N.D. | N.D. | N.D. | 15 ± 17 | >300 | 347 ± 132 |
| Acyclovir | 2.84 ± 2.36 | 1.64 ± 0.67 | 54 ± 58 | 37 ± 7 | 0.53 ± 0.43 | 0.38 ± 0.27 | ≥212 ± 59 | N.D. | N.D. | N.D. | >1000 | >444 | 918 ± 578 |
| Ganciclovir | N.D. | N.D. | N.D. | N.D. | 0.027 ± 0.005 | 0.029 ± 0.014 | 14.7 ± 8.3 | 9.1 ± 3.0 | 5.9 ± 1.7 | 1.15 ± 0.35 | ≥ 93 ± 17 | >394 | 231 ± 97 |
| Cidofovir | N.D. | N.D. | N.D. | N.D. | 0.93 ± 0.45 | 1.33 ± 0.89 | 1.75 ± 0.42 | 1.37 ± 0.51 | 0.92 ± 0.25 | N.D. | 14.0 ± 6.2 | >317 | 241 ± 260 |
EC50: 50% effective concentration or compound concentration required to reduce virus induced cytopathic effect by 50%.
CC50: 50% cystostatic concentration or compound concentration required to reduce cell growth by 50%.
MCC: minimum cytotoxic concentration or the compound concentration that caused a microscopically detectable alteration of cell morphology.
Selectivity index (SI): ratio CC50 to EC50.
N.D.: not done.
a
Assays performed in CRFK (Crandell-Rees feline kidney) cells.