TABLE 2.
In vitro activity of analogs with dideoxy and D4 pseudosugars against HIV-1 RT with the K65R mutation
| Compounda | Mean IC50 (μM) ± SDb
|
P | ||
|---|---|---|---|---|
| HIV-1WT | HIV-165R | Fold increasec | ||
| ddC | 1.35 ± 0.70 | 6.79 ± 3.98 | 5.0 | <0.0001 |
| ddG | 3.11 ± 0.64 | 12.5 ± 1.5 | 4.0 | <0.0001 |
| ddI | 2.32 ± 0.98 | 6.26 ± 2.92 | 2.7 | <0.0001 |
| ddTd | 10.2 ± 4.8 | 22.3 ± 9.3 | 2.2 | 0.01 |
| d4C | 2.63 ± 1.20 | 17.9 ± 6.4 | 6.8 | <0.0001 |
| d4T | 5.72 ± 3.34 | 21.8 ± 23.8 | 3.8 | <0.001 |
| d4FC | 1.26 ± 0.51 | 14.6 ± 7.1 | 12 | <0.0001 |
| 2′-F-d4A | 2.19 ± 0.91 | 4.35 ± 1.4 | 2.1 | <0.01 |
| 2′-F-d4FCd | 7.35 ± 5.6 | 84.5 ± 9.6 | 11.5 | 0.001 |
| L-d4FC | 0.23 ± 0.14 | 1.20 ± 0.17 | 5.2 | 0.005 |
a
Compounds are d-enantiomers except for L-d4FC.
b
Means ± standard deviations from at least three independent experiments. All assays were done with P4/R5 cells and a single-replication-cycle assay unless otherwise noted.
c
Fold increase in IC50 relative to wild-type results.
d
Assay done with MT-2 cells (see Materials and Methods).