TABLE 3.
Activities of compounds against viruses resistant to HIV-1-specific inhibitors
| Drug(s) to which isolates are resistant (mutation) | EC50 (μM)a
|
||||
|---|---|---|---|---|---|
| Calanolide A | Costatolide | Dihydrocostatolide | Nevirapine | AZT | |
| IIIB (control) | 0.1 | 0.2 | 0.2 | 0.01 | 0.05 |
| Oxathiin carboxanilide (L100I) | >27 | >270 | >20 | 0.1 | 0.04 |
| UC10-costatolide (K103N) | >27 | >270 | >20 | NDb | 0.003 |
| Thiazolobenzimidazole (V108I) | 24.0 | 4.4 | 3.5 | 0.3 | 0.04 |
| TIBO-R82150 (A98G-V108I) | 22.0 | 1.6 | 5.1 | 0.6 | 0.05 |
| Calanolide A (T139I) | >27 | 4.5 | >20 | 0.01 | 0.01 |
| Diphenylsulfone (Y181C) | 0.08 | 0.08 | <0.01 | 5.9 | 0.01 |
| Nevirapine (Y181C) | <0.01 | <0.01 | 0.09 | >38 | 0.03 |
| Pyridinone (Y181C-L103N) | 0.12 | 0.8 | 0.8 | >38 | 0.01 |
| E-BPTU (Y181C) | 0.1 | <0.08 | <0.06 | 1.9 | 0.03 |
| UC38 (Y181C) | 0.2 | <0.03 | 0.1 | 1.9 | 0.01 |
| 3TC (M184V) | 0.3 | 1.3 | 1.0 | 0.01 | 0.02 |
| Costatolide (Y188H) | >27 | >27 | >27 | ND | 0.004 |
| HEPT (P236L) | 0.6 | 1.1 | 0.2 | 0.02 | 0.01 |
a
EC50s are the means for a minimum of two replicate evaluations. The reproducibilities of the EC50s obtained between replicate experiments in this highly optimized anti-HIV assay have been determined to be such that the standard errors averaged less than 10% of the respective mean value. EC50s indicated as greater than indicate that the compound was inactive at greatest nontoxic concentration tested.
b
ND, not determined.