TABLE 1.
Metabolic properties of CDV, (S)-HPMPA, and their hexadecyloxypropyl esters and antiviral activity against vaccinia virus strain Copenhagen in vitroa
| Drug | Cell uptake
|
Anabolic phosphorylation
|
Antiviral activity
|
|||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Drug concn (μM) | Mean uptake (pmol/well) ± SDb | Source or reference | Drug concn (μM) | N | Np | Npp | Source or reference | Mean EC50 (μM) ± SDb | Source or reference | |
| CDV | 3.0 | 3.60 ± 0.29 (3) | 1 | 10 | 274 | 1.0 | 1.3 | 1 | 46 ± 12 (2) | 20 |
| HDP-CDV | 3.0 | 187 ± 12.0 (2) | 1 | 10 | 697 | 63 | 132 | 1 | 0.80 ± 0.40 (2) | 20 |
| (S)-HPMPA | 3.0 | 2.77 ± 0.20 (4) | This study | 10 | 29 | 6.0 | 21 | This study | 2.70 ± 2.40 (2) | 5 |
| HDP-(S)-HPMPA | 3.0 | 155 ± 16 (4) | This study | 10 | 93 | 68 | 451 | This study | 0.01 ± 0.004 (2) | 5 |
a
Drug uptake was measured in MRC-5 fibroblasts in 24-well plates 24 h after each compound was added to the culture media. Anabolic phosphorylation was assessed in MRC-5 cells grown in T-75 flasks, 24 h after the addition of 14C-labeled versions of each compound. Abbreviations: N, nucleotide; Np, nucleotide monophosphate; Npp, nucleoside diphosphate.
b
Values in parentheses are the numbers of independent replicates.