Table 1.

Inhibition of supercoiling by WT and mutant gyrase with a range of quinolones  

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CompoundaYbXcIC50(μM) for WTFold increase in IC50 for mutantd
No.NameAla83Ala87Ala83Ala87
1CiprofloxacinCHC3H5 e 1.1 ± 0.233.0 ± 0.74.6 ± 0.438.3 ± 0.9
2PD0117962CFC3H5 0.7 ± 0.062.7 ± 0.34.0 ± 0.529 ± 2.8
3PD0164488COEthC3H5 1.7 ± 0.243.7 ± 0.64.1 ± 0.425 ± 0.8
4PD0129603CClC3H5 0.8 ± 0.072.9 ± 0.33.1 ± 0.69 ± 1.2
5PD0163449CBrC3H5 0.9 ± 0.123.1 ± 0.23.5 ± 0.19 ± 1.3
6NorfloxacinCHC2H5 4.8 ± 1.064.6 ± 1.06.6 ± 1.078 ± 1.8
7EnoxacinNC2H5 4.4 ± 0.625.8 ± 1.115.1 ± 2.9>2,000
8PD0117731CFC2H5 2.0 ± 0.382.7 ± 0.13.6 ± 0.331 ± 2.1
9Ofloxacin3.5 ± 0.602.7 ± 0.13.1 ± 0.317 ± 1.0
  • a Compounds 1 through 8 have structure A, while compound 9 has structure B.

  • b C-8.

  • c N-1.

  • d Relative to that for WT; calculated as IC50 for mutant divided by IC50 for WT.

  • e Cyclopropyl form.