Table 1.
Cruzain inhibition and trypanocidal activity of compounds with modifications to the imide nucleus.
 | |||
|---|---|---|---|
| Compound | Structure | IC50 cruzain (μM)a | IC50 T. cruzi (μM)b |
| Initial hit (3a) |  |
2.2 ± 0.4 | >100 |
| 10b |  |
4.2 ± 1.5 | >100 |
| 10c |  |
2.3 ± 1.0 | 0.9 ± 0.3 |
| 10d |  |
12.0 ± 1.0 | 18.5 ± 3.1 |
| 10e |  |
2.5 ± 0.6 | 1.2 ± 0.3 |
| 10f |  |
0.6 ± 0.1 | 2.0 ± 0.7 |
| 10k |  |
ND | >100 |
| 10l |  |
ND | 11.6 ± 2.4 |
| 10m |  |
ND | 1.8 ± 0.4 |
| 10n |  |
ND | 1.6 ± 0.5 |
| 10o |  |
ND | 1.7 ± 0.5 |
| BZ | - | ND | 3.0 ± 0.6 |
a
IC50 values against cruzain were independently determined by obtaining rate measurements in triplicate for at least six inhibitor concentrations. The values represent the mean ± SD of three individual experiments.
b
IC50 values against T. cruzi represent the mean ± SD of two individual experiments. ND, not determined.