Table 1.
Biological Activity of Analogs of Thiostrepton (See Supporting Information for details and additional data)
| Compound (Ar substituent) | MIC (ug/mL) for a range of organisms (VSE = Vancomycin susceptible, VRE = vancomycin resistant) | |||||
|---|---|---|---|---|---|---|
| S. aureus MRSA | E. faecalis VSE | E. faecalis VRE | E. faecium VRE | S. pneumoniae PSSP | S. pyogenes | |
| Thiostrepton 1 | 0.25 | 0.5 | 0.25 | 0.12 | 0.002 | 0.002 |
| Vancomycin | 1 | 2 | >32 | >32 | 0.25 | 0.5 |
| 2A (4-OMe) | 1 | 1 | 1 | 1 | 0.008 | 0.004 |
| 2A’ (4-OMe) | 0.5 | 1 | 0.5 | 0.25 | 0.002 | 0.002 |
| 4A (4-F) | 1 | 1 | 1 | 0.5 | 0.008 | 0.008 |
| 4A’ (4-F) | 2 | 2 | 1 | 1 | 0.015 | 0.008 |
| 5A (3-CF3) | 2 | 1 | 1 | 1 | 0.008 | 0.004 |
| 5A’ (3-CF3) | 2 | 1 | 1 | 0.5 | 0.008 | 0.004 |
| 6A (4-Cl) | 2 | 1 | 1 | 1 | 0.015 | 0.004 |
| 6A’ (4-Cl) | 2 | 2 | 1 | 1 | 0.008 | 0.004 |
| 7A (4-Me) | 2 | 1 | 0.5 | 0.5 | 0.004 | 0.002 |
| 8A (4-′Bu) | 4 | 2 | 2 | 2 | 0.008 | 0.008 |
| 8A’ (4-′Bu) | 8 | 4 | 2 | 2 | 0.03 | 0.015 |
| 9A (4-OCF3) | 2 | 1 | 2 | 1 | 0.008 | 0.008 |
| 10A (4-Morph.) | 4 | 2 | 2 | 1 | 0.015 | 0.015 |
| 10A’ (4-Morph.) | 2 | 1 | 1 | 0.5 | 0.008 | 0.004 |
| 11A (Benzofuran) | 2 | 2 | 1 | 1 | 0.008 | 0.004 |
| 11A’ (Benzofuran) | 4 | 2 | 4 | 2 | 0.015 | 0.015 |
| 12A (Dibenzofuran) | 2 | 2 | 2 | 1 | 0.008 | 0.008 |
| 14A (Dansyl) | 32 | 4 | 8 | 2 | 0.03 | 0.03 |
| 14A’ (Dansyl) | 64 | 4 | 4 | 2 | 0.15 | 0.15 |