Table 1.
Anti-HIV-1 activity and cytotoxicity of tested NRTIs
| Anti-HIV-1 IC50(nM) against | CC50 (μM) in MT-4 | S.I. with (CC50/IC50WT) |
|||||
|---|---|---|---|---|---|---|---|
| Compound | HIV-1WT | HIV-1K65R | HIV-167-75a | HIV-1M184V | HIV-1T215F | ||
| FMAdA | 3.0 ± 1.8 | 2.7 ±0.5 (0.9) | 6.9 ±3.6 (2.3) | > 1,000 (> 333.3) | 3.2 (1.1) | 22.2 ±4.1 | 7,400 |
| FMFdA | 24.8 ± 4.0 | 110.0 ±7.0 (4.4) | 299.5 ±126.9 (12) | > 1,000 (>40.3) | 274.6 ± 195.3 (11.1) | 6.6 ±0.5 | 260 |
| MAdA | 247.0 ±57.5 | 97.1 ±75.6 (0.4) | 209.0 ±40.0 (0.8) | > 1,000 (> 4) | 139.2 ±39.2 (0.6) | 4.0 ±0.3 | 15 |
| VAdA | 4.3 ±1.4 | 5.4 ±6.5 (1.3) | 7.8 ±1.3 (1.8) | > 1,000 (>232.6) | 7.9 (1.8) | 20.6 ±3.2 | 4,790 |
| EtAdA | 8.9 ±3.5 | 10.2 ± 13.7 (El) | 31.6 ±13.7 (3.6) | > 1,000 (> 112.4) | 25.9 ±6.1 (2.9) | 35.9 ± 3.1 | 4,030 |
| EtdG | 5.6 ±0.2 | 14 (2.5) | 25.6 ±7.6 (4.6) | > 1,000 (> 178.6) | 19.9 ±3.1 (3.6) | 47.0 ±3.2 | 8,390 |
| MdG | 170.8 ±35.6 | 189.2 ±75.2 (El) | 281.5 ±34.5 (1.6) | > 1,000 (> 5.9) | 184.8 ±72.0 (1.1) | 4.6 ±0.6 | 25 |
| FMAMdA | 164.8 ±8.6 | 132.9 ±7.2 (0.8) | 321.4 ±65.5 (2.0) | > 1,000 (> 6.1) | 189.0 ±68.5 (1.1) | > 100 | >600 |
| EdG | 1.6 ±0.2 | 0.1 ±0.06 (0.06) | 1.8 ± 0.1 (1.1) | 4.4 ±3.2 (2.8) | 2.0 ±0.6 (1.3) | 7 | 4,350 |
| CdT | 9.1 ±7.3 | 2.0 ±0.01 (0.2) | 8.6 ±5.9 (0.9) | 11.7±2.4 (1.3) | 3.0 (0.3) | > 10 | > 1,100 |
| FMdC | 32.9 ± 10.7 | 34.6 ± 3.6 (E0) | 28.4 ±6.2 (0.9) | > 1,000 (> 30.4) | 24.3 ±15.5 (0.7) | 4 | 120 |
| EdC | 25.2 ±4.3 | 10.2 ±4.0 (0.4) | 31.6 ± 9.9 (1.3) | 15.5 ± 1.7 (0.6) | 30.0 ± 13.9 (1.2) | N.D. | N.D. |
| EdI | 276.1 ±58.6 | 37.1 ±3.2 (0.1) | 294.3 ±48.3 (1.1) | 356.2 ±77.2 (1.3) | 297.7 ±96.3 (1.1) | N.D. | N.D. |
| CAdA | 0.2 ±0.1 | 0.6 ±0.3 (3) | 2.6 ±0.2 (13) | 4.4 ±3.2 (22) | 1.2 ±0.9 (6) | 3.5 ± 1.2 | 17,500 |
| EFdA | 0.3 ±0.2 | 0.8 ±0.3 (2.7) | 3.0 ±1.5 (10) | 3.7 ±1.7 (12.3) | 2.3 ±0.01 (1.7) | 19.2 ±6.0 | 64,000 |
| AZT | 37.4 ±7.5 | 13.5 ±1.0 (0.4) | 230.1 ±65.8 (6.2) | 16.8 ±12.8 (0.4) | 114.0 ±88.3 (3.0) | > 100 | > 2,670 |
| ABC | 262.9 ±7.6 | 1,512.2 ±704.6 (5.8) | 2,750.5 ±390.0 (10.5) | 1,525.6 ±431.1 (5.8) | 1,673.4 ±72.4 (6.4) | > 100 | >380 |
| TDF | 203.9 ±126.6 | 2,249.1 ± 1596.8 (1E0) | > 1,000 (> 4.9) | 422.8 ±112.6 (2.0) | N.D. | 39.4 ±7.3 | 190 |
Abbreviations: IC50 : 50% inhibitory concentration, CC50 : 50% cytotoxic concentration, S.I.: selectivity index. (CC50/ IC50), N.D.: not determined.
Anti-HIV-1 activity was determined using MT-4 cells by MTT assay. Each assay was conducted in duplicate or triplicate. The values represent mean values (± 1 S.D.) out of two or three independent experiments. See also Supp. Tables S1 and S2.
a
67Δ/T69G/K70R/L74I/V75T.