TABLE 1.
Physicochemical and microbiological data for quinolone amide compounds
| Compound | Mol wt (g/mol) | LogP | Preliminary kinetic solubility (μM) | Melting point (°C) | Albumin binding (%) | IC50 (μM) at: |
CC50a (μM) |
||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| 48 h/72 h for T. b. brucei | 72 h for T. b. rhodesiense | L6 | J774.1A | HEK 293T | HepG2 | ||||||
| GHQ168b | 437.5 | 3.67 | <19 | 171.4 | 80.5 | 0.047 ± 0.00/0.05 ± 0.01 | 0.001 ± 0.0006 | 47.2 ± 9.7 | 57 | 26.30 ± 5.35 | 47.04 ± 3.04 |
| GHQ237 | 420.5 | 3.05 | 100 | 178.1 | 67.6 ± 4.53 | 0.55 ± 0.08/1.02 ± 0.33 | 0.012 ± 0.0025 | >95.2 | >100 | >160 | >160 |
| GHQ242 | 438.5 | 1.74 | >5,000 | 149.0 | 99.95 ± 0.02 | 0.29 ± 0.26/0.76 ± 0.77 | 0.002 ± 0.0004 | 24.3 ± 4.2 | >100 | 86.81 ± 6.43 | 153.31 ± 9.47 |
| GHQ243 | 452.5 | 2.67 | 1,000 | 198.2, 223.0 | 45.9 ± 4.19 | 0.54 ± 0.01/0.63 ± 0.01 | 0.018 ± 0.0094 | 30.7 ± 7.4 | 42.3 | 48.03 ± 1.94 | 48.84 ± 0.12 |
| GHQ250 | 524.6 | 3.41 | >5,000 | 172.3 | 79.1 ± 7.42 | 2.89 ± 0.62/3.37 ± 0.29 | NDc | ND | 39.9 | 10.25 ± 1.56 | 13.12 ± 0.03 |
| GHQ232 | 436.5 | 3.47 | 100 | >300 | 85.8 ± 5.27 | 9.08 ± 0.12/15.05 ± 1.79 | ND | ND | 39.1 | 13.98 ± 0.64 | 19.34 ± 2.91 |
| GHQ215 | 453.5 | 5.53 | 10 | >300 | ND | 3.08 ± 0.69/5.73 ± 0.91 | ND | ND | >100 | 26.59 ± 5.29 | >160 |
a
CC50, 50% cytotoxic concentration.
b
Most of the data for GHQ168 were already reported in reference 9 (see compound 29).
c
ND, not determined.