Table 1.
Anti-HIV activities of DAANs against wild-type and drug-resistance viral stains
| |||||
|---|---|---|---|---|---|
| Cmpd | R1 | EC50 nM (FCa)
|
CC50 nMg | ||
| NL4-3b | E138Kc | E138K+M184Ic | |||
| 8a | -CO2(CH2)2OCH3 | 1.52 ± 0.31 | 4.56 ± 0.35 (2.9) | 9.54 ± 3.73 (6.3) | >207 |
| 8b | -CO2(CH2)2CN | 1.11 ± 0.29 | 2.94 ± 0.40 (2.4) | 4.61 ± 1.64 (4.1) | >210 |
| 8c | -CONH(CH2)2Cl | 3.29 ± 1.13 | 8.50 ± 2.68 (2.6) | 17.3 ± 4.54 (5.2) | >206 |
| 8d | -CONH(CH2)3OH | 24.9 ± 8.51 | 22.8 ± 6.43 (0.9) | NDd | >208 |
| 8e | -CON(CH2)2 | 3.33 ± 1.40 | 8.69 ± 3.12 (2.6) | 16.7 ± 5.34 (5.0) | >223 |
| 8f | -CON(CH2)2CF2 | 13.4 ± 4.60 | ND | ND | >200 |
| 8g | -CONHNH2 | 11.6 ± 4.11 | ND | ND | >228 |
| 3e | -CONH2 | 1.82 ± 0.57 | 3.55 ± 0.64 (1.9) | 3.55 ± 1.02 (1.9) | >23,600 |
| 4ae | -CONHCH3 | 2.50 ± 0.66 | 3.87 ± 1.23 (1.6) | 5.24 ± 1.62 (2.1) | >9100 |
| 4bf | -CONHEt | 6.18 ± 1.41 | 12.1 ± 3.09 (2.0) | 8.61 ± 1.83 (1.4) | 105,000 |
| 4ce | -COOCH3 | 1.57 ± 0.50 | 2.95 ± 0.86 (1.9) | 3.64 ± 0.75 (2.3) | >22,700 |
| 2 | 0.44 ± 0.11 | 3.55 ± 0.85 (8.1) | 2.38 ± 0.71 (5.4) | >273 | |
a
Resistance fold change (FC) is the ratio of EC50(resistant viral strain) / EC50(wild-type viral strain).
b
HIV-1 with wild-type reverse transcriptase.
c
Resistant viral strains.
d
Not detected.
e
Compound reported in Ref. 8.
f
Compound reported in Ref. 12.
g
The highest tested concentration of 8a–8g was 100 ng/mL with at least three experiments (n = 3).