Table 2.
Inhibitory activity of 4a-4g and 5a-5g on HIV-1NL4-3 and HIV-1RTMDR-1 replication in TZM-bl cells. *
| NL4-3 | RTMR1a | |||||
|---|---|---|---|---|---|---|
| Cmpd | R | CC50 (μM) |
EC50 (μM) |
SI | EC50 (μM) |
SI |
| 4a | H | >55.56 | 0.234±0.058 | >238 | 0.128±0.031 | >433 |
| 4b | CH3 | >53.48 | 0.0229±0.0052 | >2,335 | 0.0552±0.0098 | >969 |
| 4c | CH2OH | >51.28 | 0.477±0.371 | >108 | 0.877±0.562 | >58 |
| 4d | I | >41.15 | 0.061±0.024 | >675 | 0.0943±0.009 | >436 |
| 4e | CN | >51.95 | 0.0221±0.0061 | >2,351 | 0.0211±0.004 | >2,462 |
| 4f | C≡CC(OH)Me2 | >45.25 | 41.346 | >1.09 | 25.480 | >1.78 |
| 4g | C≡CH | >52.08 | 0.111±0.086 | >469 | 0.215±0.0327 | >242 |
| 5a | H | 8.14 | 0.00402±0.00058 | 2,025 | 0.00378±0.00134 | 2,153 |
| 5b | CH3 | 18.63 | 0.00167±0.00014 | 11,156 | 0.00120±0.0003 | 15,525 |
| 5c | CH2OH | 9.34 | 0.0109±0.0037 | 857 | 0.0251±0.0081 | 372 |
| 5d | I | 16.72 | 0.0076±0.0023 | 2,200 | 0.00513±0.00115 | 3,259 |
| 5e | CN | 8.98 | 0.00068±0.00003 | 13,206 | 0.00096±0.00027 | 9,354 |
| 5f | C≡CC(OH)Me2 | 8.73 | 0.241±0.0147 | 36 | 0.531 | 16 |
| 5g | C≡CH | 9.94 | 0.0067±0.0010 | 1,484 | 0.00903±0.00204 | 1,101 |
| TMC120 | >0.304 | 0.00062±0.00012 | >490 | 0.000298±0.00015 | >1,020 | |
*
The compounds were tested in triplicate and the data are presented as means ± SD.
a
HIV-1RTMDR1 (obtained from AIDS Research and Reference Reagent Program, Division of AIDS, NIAID, NIH), which contains mutations in RT amino acid residues 74V, 41L, 106A, and 215Y, is resistant to AZT, ddI, nevirapine, and other non-nucleoside RT inhibitors.