Table 3.
The effect of type I Nitroreductase (TbNTR) on the activity of selected compounds against bloodstream-form T. brucei brucei parasites.
| ID No | T.b. bruceia | TbNTRb | TbNTRb | Ratio | E1/2c |
|---|---|---|---|---|---|
| IC-50 (μM) | -tet | +tet | -tet/+tet | (V) | |
| 8 | 7.47 ± 0.71 | 7.58 ± 0.19 | 0.95 ± 0.11 | 8.00 | -1.03 |
| 17 | 0.17 ± 0.04 | 0.44 ± 0.06 | 0.10 ± 0.04 | 4.00 | -1.18 |
| 20 | 2.63 ± 0.25 | 4.48 ± 0.19 | 0.07 ± 0.02 | 64.00 | -1.04 |
| 23 | > 10 | nd | nd | nd | nd |
| 29 | 7.83 ± 0.32 | 11.08 ± 2.50 | 0.76 ± 0.16 | 14.00 | -1.07 |
| 38 | 0.21 ± 0.01 | 0.20 ± 0.01 | 0.10 ± 0.02 | 2.00 | -1.06 |
| 40 | > 10 | nd | nd | nd | nd |
| 41 | > 10 | nd | nd | nd | -1.04 |
| 42 | 2.30 ± 0.10 | 2.63 ± 0.12 | 0.21 ± 0.01 | 13 | nd |
| Nifurtimoxd | 1.71 ± 0.06 | 0.13 ± 0.04 | 13 | -0.88 | |
a
Bloodstream form wild type T. brucei brucei parasites;
b
bloodstream form T. b. brucei, engineered to over-express type I nitroreductase in the presence of tetracycline (tet).
C
Reduction potential of each compound was measured in DMSO (except for 17, in CH3CN) by cyclic voltammetry relative to Ag/AgCl.
d
The E1/2 value is taken from ref. [32].