TABLE 1.
Effect of C-8 substituents on inibition of growth by fluoroquinolones
| Fluoroquinolonea | C-7 ring alkyld |
M. smegmatisb
|
S. aureusc
|
||||||
|---|---|---|---|---|---|---|---|---|---|
|
gyrA+
|
gyrA
|
parC+gyrA+
|
parC gyrA
|
||||||
| MIC99 (μg/ml)e | MIC(C-8-H)f MIC(C-8-X) | MIC99 (μg/ml) | MIC(C-8-H) MIC(C-8-X) | MIC99 μg/ml) | MIC(C-8-H) MIC(C-8-X) | MIC99 (μg/ml) | MIC(C-8-H) MIC(C-8-X) | ||
| Ciprofloxacin (H) | None | 0.25 | 5.4 | 0.10 | 23 | ||||
| PD129603 (Cl) | None | 0.08 | 3.1 | 1.0 | 5.4 | 0.065 | 1.6 | 2.7 | 8.5 |
| PD138032 (H) | Me | 0.10g | 2.8 | 0.12 | 21 | ||||
| PD125275 (F) | Me | 0.036g | 2.8 | 1.2 | 2.3 | 0.1 | 1.2 | 7.3 | 2.9 |
| PD163753 (Br) | Me | 0.032g | 3.1 | 0.96 | 2.9 | 0.066 | 1.8 | 2.9 | 7.2 |
| PD138124 (Cl) | Me | 0.029g | 3.4 | 0.66 | 4.2 | 0.056 | 2.1 | 2.4 | 8.7 |
| PD135432 (OMe) | Me | 0.030g | 3.3 | 0.49 | 5.7 | 0.05 | 2.4 | 2.5 | 8.4 |
| PD158804 (H) | di-Me | 0.043 | 2.9 | 0.12 | 29 | ||||
| PD125232 (F) | di-Me | 0.049 | 0.88 | 1.2 | 2.5 | 0.15 | 0.81 | 14 | 2.1 |
| Bay y 3114 (H) | NA | 0.06 | 1.2 | 0.022 | 14 | ||||
| Moxifloxacin (OMe) | NA | 0.08 | 0.75 | 0.8 | 1.5 | 0.035 | 0.63 | 1.7 | 8.5 |
| Sparfloxacinh (F) | di-Me | 0.07 | 1.3 | 0.038 | 9 | ||||
Parenthetical information indicates moiety at the C-8 position. PD135432 is identical to gatifloxacin. OMe, methoxy.
M. smegmatis strains were mc2 155 (gyrA+) and KD2003 (gyrA).
S. aureus strains were ISP794 (gyrA+ parC+) and EN1252 (gyrA parC); in S. aureus parC was originally termed grlA.
Alkyls attached to C-7 ring carbon. NA, not applicable because the C-7 ring systems are not comparable to other members of the set (see Fig. 1).
Identical results for each MIC99 were obtained for two independent determinations.
MIC99 for the C-8-H fluoroquinolone of each series having a given C-7 ring structure, divided by MIC99 for indicated compounds having C-8 substitutents, where X = F, Br, Cl, or OMe (methoxy) groups.
Data taken from reference (26).
Identical to PD125232 but with additional C-5 NH2.