TABLE 2.
Effect of C-8 substituents on lethal action of fluoroquinolones
| Fluoroquinolonea | C-7 ring alkylb | LD90 (μg/ml)c
|
|||
|---|---|---|---|---|---|
|
M. smegmatis
|
S. aureus
|
||||
| gyrA+ | gyrA | parC+ gyrA+ | parC gyrA | ||
| Ciprofloxacin (H) | 0.6 | >120 | 0.28 | >320 | |
| PD129603 (Cl) | 0.19 | 11 | 0.07 | 9.4 | |
| PD1380232 (H) | Me | 0.38 | >120 | 0.34 | 320 |
| PD125275 (F) | Me | 0.29 | 12 | 0.27 | >320 |
| PD163753 (Br) | Me | 0.38 | 7.2 | 0.23 | 7.5 |
| PD138124 (Cl) | Me | 0.25 | 9.0 | 0.32 | 9.0 |
| PD135432 (OMe) | Me | 0.22 | 8.0 | 0.21 | 7.3 |
| PD158804 (H) | di-Me | 0.37 | >120 | 0.47 | >320 |
| PD125232 (F) | di-Me | 0.36 | 100 | 0.31 | 35 |
| Bay y 3114 (H) | NA | 0.15 | 120 | 0.07 | >320 |
| Moxifloxacin (OMe) | NA | 0.28 | 12 | 0.08 | 5.2 |
a
Parenthetical information indicates moiety at the C-8 position. PD135432 is identical to gatifloxacin. OMe, methoxy.
b
Alkyls attached to C-7 ring. NA, not applicable because the C-7 ring systems are not comparable with other members of the set (see Fig. 1).
c
Concentration required to reduce survival by 90% as determined from Fig. 2 to 5. Similar results were obtained in two independent experiments. The S. smegmatis strains were mc2155 (gyrA+) and KD2003 (gyrA); the S. aureus strains were ISP794 (parC+ gyrA+) and EN1252 (parC gyrA). In S. aureus parC was originally designated grlA.