Table 1.
E. coli topoisomerase I inhibition and whole cell antibacterial activities (µM) of fluoroquinophenoxazine derivativesa
| Topoisomerase inhibitory activity (IC50, µM) | Whole cell based antibacterial activity (MIC, µM) | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Compd |
E. coli topo I (type IA) |
E. coli DNA gyrase (type IIA) |
Human topo I (type IB) |
Human topo IIα (type IIA) |
E. coli Imp4213 (BAS3023) |
E. coli (MG1655) WT |
B. subtilis (ATCC 6633) WT |
M tuberculosis (H37Rv) |
Vero cell IC50 |
SIb |
| 1 | 1.95 | >125 | 31.3 | >500 | 0.78–1.56 | >200 | 6.25 | 11.2 | 75.7 | 6.8 |
| 6a | 15.6 | 50 | >200 | 25 | ||||||
| 6b | 31.25 | >200 | >200 | 200 | ||||||
| 6c | >125 | >200 | >200 | >200 | ||||||
| 7a | 15.6 | 0.78 | 200 | 12.5 | ||||||
| 7b | 31.25 | 200 | >200 | >200 | ||||||
| 7c | >125 | >200 | >200 | 25 | ||||||
| 7d | 15.6 | >200 | >200 | >200 | ||||||
| 7e | 31.25 | 62.5 | 31.25 | 125 | 0.39 | 50 | 3.12 | 29 | >127 | >4.4 |
| 9 | 1.95 | 25 | >200 | 50 | ||||||
| 10a | 1.95 | 62.5–125 | 31.25 | 250–500 | 1.56 | 100 | 0.78 | 19 | 95 | 5.0 |
| 10b | 3.9 | >200 | >200 | >200 | ||||||
| 11a | 0.48 | 15.6–31.25 | 15.6 | 3.9–7.8 | 0.78 | 6.25 | 0.78 | 7.6 | 29 | 3.8 |
| 11b | 0.24 | 7.8–15.6 | 7.8 | 1.95–3.9 | 0.39 | >200 | 25 | 29.5 | >126 | >4.3 |
| 11c | 3.9 | 3.12 | >200 | 0.78 | ||||||
| 11d | 0.97 | 7.8 | 15.6 | 15.6 | 0.19–0.39 | >200 | 0.19 | 3.5 | 24.7 | 7.1 |
| 11e | 3.9 | 50 | >200 | 25–50 | ||||||
| 11f | 3.9–7.8 | 3.12 | >200 | 12.5 | 38.4 | 30.7 | 0.8 | |||
| 11g | 0.48 | 15.6 | 3.9 | 1.95–3.9 | 0.39–0.78 | >200 | 1.56 | 2.5 | 24.4 | 9.8 |
| 11h | 0.97 | 15.6–31.25 | 7.8–15.6 | 3.9–7.8 | 0.78 | >200 | 1.56 | 21.6 | 43.0 | 2.0 |
| 11i | 3.9 | 25 | >200 | 12.5 | ||||||
| 11j | 3.9 | 25 | >200 | 12.5 | ||||||
| 11k | 15.6 | >200 | >200 | >200 | ||||||
| 12 | 7.8 | >200 | >200 | >200 | ||||||
| 15a | 3.9 | 12.5 | >200 | 12.5 | ||||||
| 16 | 0.48 | 3.9 | 7.8 | 1.95–3.9 | 1.56 | >200 | 0.78 | >50 | >50 | |
| 17a | 0.48–0.97 | 3.9 | 3.9 | 0.97–1.95 | 1.56 | >200 | 6.25 | >63.1 | >63.1 | |
| 17b | 0.48–0.97 | 3.9 | 3.9 | 3.9 | 6.25 | >200 | 12.5 | >63.1 | >63.1 | |
a
Blank cells indicate Not Determined.
b
Selectivity index = cytotoxic IC50 against Vero cells/MIC against M. tuberculosis.