TABLE 1.
Structural features and concentrations of quinolones inhibiting M. leprae DNA gyrase activity and M. leprae growtha
| Quinolone | R-1 | R-6 | R-7 | N- or C-8 | In vitro studies
|
Mouse MIC (mg/kg/day)c from in vivo studies | ||
|---|---|---|---|---|---|---|---|---|
| IC50 (μg/ml) | CC25 (μg/ml) | MGIb | ||||||
| Sitafloxacin | Fluorinated cyclopropyl | F | Pyrrolidine | C-Cl | 1 | 0.5 | ND | 25d |
| Gatifloxacin | Cyclopropyl | F | Piperazine | C-OCH3 | 2 | 1 | ND | ND |
| Moxifloxacin | Cyclopropyl | F | Azabicyclo | C-OCH3 | 2 | 2 | ND | 150e |
| Clinafloxacin | Cyclopropyl | F | Pyrrolidine | C-Cl | 3 | 0.6 | ND | ND |
| Ciprofloxacin | Cyclopropyl | F | Piperazine | C-H | 3.5 | 2.5 | 32 | >150f |
| Garenoxacin | Cyclopropyl | H | Azabicyclo | C-OCHF2 | 3.5 | 3 | ND | ND |
| Sparfloxacin | Cyclopropyl | F | Piperazine | C-F | 5 | 1 | ND | 15g |
| Levofloxacin | Bridge C-1-C-8 | F | Piperazine | Bridge C-1-C-8 | 7 | 3 | ND | ND |
| Ofloxacin | Bridge C-1-C-8 | F | Piperazine | Bridge C-1-C-8 | 10 | 10 | 20 | 150h |
| Pefloxacin | Ethyl | F | Piperazine | C-H | 23 | 40 | 29 | >300g |
| Temafloxacin | Difluorophenyl | F | Piperazine | C-H | 26 | 11 | 29 | 50g |
| Oxolinic acid | Ethyl | Bridge C-6-C-7 | Bridge C-6-C-7 | H | 170 | No | ND | ND |
| Nalidixic acid | Ethyl | H | CH3 | N | 300 | No | ND | ND |
a
ethyl, C2H5; cyclopropyl, c-C3H5; difluororophenyl, 2′,4-F-C3H5; No, not observed; ND, not determined.
b
MGI, mean growth index from days 11 to 18 at 5 μg/ml of drug determined with the BACTEC 460 system against M. leprae (10).
c
Dosage of quinolones given to mice infected with leprosy leading to a fully bactericidal effect (>99% of the M. leprae organisms were killed) even 9 months after the completion of therapy, expressed as mg of drug per kg of mouse body weight per day.
d
Datum from Dhople et al. (9).
e
Datum from Consigny et al. (8).
f
Datum from Guelpa-Lauras et al. (15).
g
Data from Gelber et al. (11).
h
Datum from Grosset et al. (14).