TABLE 2.
Effect of various aminocoumarins on E. coli DNA gyrase in vitro and on growth of selected microorganisms
| Compound | DNA gyrase inhibition ratio (IC50nov/ IC50comp)a | Bioassay with B. subtilis (relative activity [%]) | Growth inhibition (MIC [μg/ml]) of:
|
|||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S. aureus ATCC 29213 | S. aureus 42080 | S. epider- midis CNS184 | S. aureus 80CR5 | S. epider- midis CNS10 | E. faecalis ATCC 29212 | E. faecalis Van B E80-8 | E. faecium ATCC 19434 | E. faecium Van A E25-1 | S. pneumo- niae 1/1 (serotype 6) | E. coli UB1005 | E. coli DC2 | P. aeru- ginosa K799/wt | P. aeru- ginosa K799/61 | |||
| Novobiocin | 1.00 | 300 | ≤0.06 | 0.25 | ≤0.06 | >32 | 4 | 16 | 16 | >32 | 2 | 8 | >32 | 4 | >32 | 2 |
| Clorobiocin | 3.52 | 100 | ≤0.06 | ≤0.06 | ≤0.06 | 4 | 0.125 | 2 | 4 | >32 | 0.25 | 2 | >32 | 2 | 32 | ≤0.06 |
| Clorobiocin derivatives | ||||||||||||||||
| 211 | 0.91 | 50-100 | ≤0.06 | ≤0.06 | ≤0.06 | 8 | 0.25 | 16 | 16 | >32 | 8 | 8 | >32 | 4 | >32 | 0.5 |
| 221 | 1.83 | 25-50 | ≤0.06 | ≤0.06 | ≤0.06 | 32 | 1 | ≥32 | 32 | >32 | 16 | 8 | >32 | 8 | >32 | 0.5 |
| 231 | 1.75 | 25 | ≤0.06 | 0.125 | ≤0.06 | 32 | 2 | >32 | >32 | >32 | 16 | 16 | >32 | 16 | >32 | 1 |
| 241 | 0.86 | 6-12.5 | 4 | 4 | 0.125 | >32 | 16 | >32 | >32 | >32 | >32 | >32 | >32 | >32 | >32 | 2 |
| 251 | 0.84 | 12.5 | 1 | 0.5 | ≤0.06 | >32 | 8 | >32 | >32 | >32 | >32 | >32 | >32 | >32 | >32 | 1 |
| 261 | 1.65 | 12.5 | 2 | 1 | ≤0.06 | >32 | 4 | >32 | >32 | >32 | >32 | >32 | >32 | >32 | >32 | 1 |
| 271 | 1.85 | 12.5-25 | 1 | 1 | ≤0.06 | >32 | 4 | >32 | >32 | >32 | >32 | 32 | >32 | 32 | >32 | 0.5 |
| 281 | 0.87 | 25-50 | 1 | 0.5 | ≤0.06 | 32 | 4 | >32 | >32 | >32 | >32 | >32 | >32 | >32 | >32 | 0.5 |
| 311 | 0.47 | 3-6 | 2 | 2 | 0.125 | >32 | 8 | >32 | >32 | >32 | >32 | >32 | >32 | >32 | >32 | 4 |
| 381 | 1.91 | 12.5-25 | 0.125 | 0.5 | ≤0.06 | 32 | 4 | 8 | >32 | >32 | >32 | 8 | >32 | 16 | >32 | 1 |
| Isoclorobiocin derivatives | ||||||||||||||||
| 212 | 0.46 | 6-12.5 | 0.25 | ≤0.06 | ≤0.06 | 32 | 1 | >32 | >32 | >32 | >32 | 32 | >32 | 32 | >32 | 1 |
| 222 | 0.23 | 6-12.5 | 0.25 | 0.25 | ≤0.06 | >32 | 4 | >32 | >32 | >32 | >32 | 32 | >32 | >32 | >32 | 1 |
| 232 | 0.05 | 3-6 | 1 | 2 | 0.125 | >32 | 8 | >32 | >32 | >32 | >32 | >32 | >32 | >32 | >32 | 8 |
| 242 | 0.11 | NDd | 4 | 4 | 0.5 | >32 | >32 | >32 | >32 | >32 | >32 | >32 | >32 | >32 | >32 | 4 |
| 252b | 0.21 | ND | 8 | 4 | 0.5 | >16 | >16 | >16 | >16 | >16 | >16 | >16 | >16 | >16 | >16 | 4 |
| 262 | 0.21 | ND | 2 | 2 | 0.25 | >32 | 16 | >32 | >32 | >32 | >32 | >32 | >32 | >32 | >32 | 4 |
| 272 | 0.23 | 6-12.5 | 2 | 2 | 0.25 | >32 | 8 | >32 | >32 | >32 | >32 | 32 | >32 | >32 | >32 | 2 |
| 282 | 0.11 | 6-12.5 | 2 | 2 | ≤0.06 | >32 | 8 | >32 | >32 | >32 | >32 | 32 | >32 | >32 | >32 | 2 |
| 312 | 0.47 | 3-6 | 2 | 4 | 0.25 | >32 | 8 | >32 | >32 | >32 | >32 | >32 | >32 | >32 | >32 | 8 |
| 382 | 0.48 | 6-12.5 | 0.5 | 1 | 0.125 | >32 | 16 | 16 | >32 | >32 | >32 | 8 | >32 | >32 | >32 | 4 |
| Desclorobiocin derivatives | ||||||||||||||||
| 214 | 0.48 | 3-6 | 4 | 4 | 0.5 | >32 | 16 | >32 | >32 | >32 | >32 | >32 | >32 | >32 | >32 | 32 |
| 233 | 0.23 | ND | 4 | 4 | 0.5 | >32 | 16 | >32 | >32 | >32 | >32 | >32 | >32 | >32 | >32 | 32 |
| 243 | 0.23 | ND | 16 | 32 | 2 | >32 | 16 | >32 | >32 | >32 | >32 | >32 | >32 | >32 | >32 | 32 |
| 253 | 0.11 | ND | 16 | 16 | 2 | >32 | >32 | >32 | >32 | >32 | >32 | >32 | >32 | >32 | >32 | 16 |
| 313 | 0.25 | ND | 8 | 16 | 2 | >32 | >32 | >32 | >32 | >32 | >32 | >32 | >32 | >32 | >32 | 32 |
| 383 | 0.50 | 6-12.5 | 8 | 8 | 4 | >32 | >32 | ≥32 | >32 | >32 | >32 | 32 | >32 | >32 | >32 | 8 |
| Other compounds | ||||||||||||||||
| 384c | 0.25 | 3 | 8 | 8 | 2 | >8 | >8 | >8 | >8 | >8 | >8 | >8 | >8 | >8 | >8 | 8 |
| 385 | 0.02 | <1 | >32 | >32 | >32 | >32 | >32 | >32 | >32 | >32 | >32 | >32 | >32 | >32 | >32 | >32 |
| 283 | 0.03 | ND | ND | ND | ND | ND | ND | ND | ND | ND | ND | ND | ND | ND | ND | ND |
a
IC50 for novobiocin (0.5 μM)/IC50 for compound.
b
Due to restricted availability of the compound, MICs were measured over the concentration range 0.03 to 16 μg/ml.
c
Due to restricted availability of the compound, MICs were measured over the concentration range 0.015 to 8 μg/ml.
d
ND, not determined.