Table 1.
Antiviral and cytotoxic properties of the synthesized compounds in human embryonic lung (HEL) cells.
| Compound | EC50a (HEL) (µM) |
Cytotoxicity (µM) |
|||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| HSV-1 (Kos) | HSV-2 (G) | HSV-1 TK− KOS ACVr | VZV TK+ (Oka) | VZV TK− (0 7 −1) | HCMV (AD-169) | HCMV (Davis) | Vaccinia virus | MCCb | CC50c | ||
| 1 | PMEO-DAPy | 45 ± 0 | 20 ± 0 | 54.0 ± 5.7 | 2.07 ± 0.39 | 4.72 ± 2.10 | >100 | >100 | >100 | >100 | 90.3 ± 13.8 |
| 2 | Bis(POM) | 10.0 ± 2.8 | 9.5 ± 7.8 | 14.5 ± 7.8 | 0.67 ± 0.49 | 1.26 ± 0.25 | 47.4 ± 22.2 | 36.5 ± 31.1 | ≥20 | ≥100 | 16.6 ± 1.3 |
| 3 | Mono(POM) | 39.5 ± 7.8 | 29 ± 12.7 | 54.0 ± 5.7 | 2.54 ± 0.20 | 5.91 ± 0.10 | >100 | >100 | >100 | >100 | ≥100 |
| 4 | Bis(POC) | 2.62 ± 1.43 | 1.01 ± 0.86 | 3.7 ± 3.0 | 0.32 ± 0.37 | 0.29 ± 0.19 | 90.1 ± 0 | 86.3 ± 5.4 | 160 ± 60 | >202 | 15.1 ± 10 |
| 5 | Bis(amino acid) phosphoramidate | 3.9 ± 0 | 3.46 ± 0.61 | 6.3 ± 3.4 | 0.56 ± 0 | 1.69 ± 1.04 | 28.4 ± 6.7 | 17.0 ± 8.1 | 157 ± 84 | 217 | 25.9 ± 10.9 |
| 6 | PME-5-azaCd | 39 | 103 | 68 | 100 | 40 | 195 | 147 | >398 | >398 | >200 |
| 7 | Bis(POC) | 22.0 ± 17.0 | 22.0 ± 17.0 | 22.0 ± 17.0 | 15.3 | 23.2 | 26.2 | 20 | >100 | >100 | ND |
| 8 | Mono(POC) | >100 | >100 | >100 | 48.9 | 48.9 | >100 | >100 | >100 | >100 | ND |
| 9 | Bis(POM) | 0.84 ± 0 | 1.26 ± 0.59 | 0.73 ± 0.15 | 0.65 ± 0.03 | 1.32 ± 0.50 | 3.24 ± 0.27 | 0.97 ± 0.19 | 152 ± 81 | 209 | 46.0 ± 5.9 |
| 10 | Mono(POM) sodium salt | 142 ± 25 | 142 ± 25 | 131 ± 10 | 40.7 ± 20.2 | 128 ± 12 | 123 ± 0 | 116 ± 40 | >275 | >275 | >275 |
| 12 | Bis-amidate | 32.5 ± 17.7 | 39.5 ± 7.8 | 42.0 ± 11.3 | 29.4 ± 26.0 | 26.8 ± 32.2 | 15.5 ± 6.4 | 7.5 ± 4.9 | >100 | >100 | >100 |
| 13 | Mono-amidate | >100 | >100 | >100 | >100 | >100 | >100 | >100 | >100 | >100 | >100 |
| 14 | Mono-methyl ester | >100 | >100 | >100 | >100 | >100 | >100 | >100 | >100 | >100 | >100 |
| 15 | Bis(octadecyloxyethyl) | >100 | >100 | >100 | >4 | >0.8 | >20 | >20 | >100 | 20 | ND |
| 16 | N4-Bis(octadecyloxyethyl) | >100 | >100 | >100 | 44.7 | 100 | >100 | >100 | >100 | 100 | ND |
| 17 | Mono-octadecyloxyethyl | 0.35 ± 0.21 | 0.15 ± 0.07 | 0.20 ± 0.14 | 0.32 ± 0.06 | 0.79 ± 0.38 | 1.12 ± 0.95 | 0.24 ± 0.11 | >100 | 100 ± 0 | 79.2 ± 7.1 |
| 23 | Bis(hexadecylamido-l-tyrosyl) | 0.60 0.28 | 0.40 0.28 | 0.40 0.28 | 0.58 ± 0.31 | 0.29 ± 0.22 | 2.16 ± 0.52 | 0.48 ± 0.08 | >100 | 60 ± 57 | 27.1 ± 6.3 |
| Acyclovir | 0.40 ± 0.26 | 0.18 0.11 | 54 ± 58 | 1.50 ± 0.96 | 38.9 ± 18.5 | ND | ND | >250 | >440 | >440 | |
| Brivudin | 0.04 ± 0.03 | 141 ± 27 | 45 ± 61 | 0.024 ± 0.020 | 58.8 ± 43.5 | ND | ND | 19.1 ± 15.3 | 300 | 242 ± 53 | |
| Ganciclovir | 0.04 ± 0.02 | 0.03 ± 0.01 | 0.10 ± 0.78 | ND | ND | 6.79 ± 2.71 | 2.96 ± 2.31 | >100 | >350 | ≥308 ± 99.4 | |
| Cidofovir | 2.93 ± 1.91 | 1.39 ± 0.47 | 2.66 ± 2.31 | ND | ND | 0.87 ± 0.31 | 0.76 ± 0.34 | 22.2 ± 2.9 | ≥300 | 216 ± 101 | |
a
50% effective concentration or compound concentration required reducing viral induced CPE or plaque formation by 50%.
b
Minimum cytotoxic concentration or compound concentration that caused a microscopically detectable alteration of cell morphology.
c
50% cytostatic concentration or compound concentration required reducing cell growth by 50%.
d
Data from Krecmerova et al. (Ref. 7).