Table 1.
Summary of in vitro results obtained in parasite and cell-based assays, as well as against the N-terminal and full-length constructs of LbHsp90 and hHsp90β for the 28 selected compounds.
| Ligand | Thermal shift | Cell viability |
IC50 (μM) |
KDapp (μM) |
|||||
|---|---|---|---|---|---|---|---|---|---|
| L. braziliensis | Balb-c | Selectivity index | LbHsp90 | LbHsp90N | hHsp90β | hHsp90βN | |||
| Glb01 | No | No | – | – | – | – | – | – | – |
| Glb02 | Yes | No | – | – | – | – | – | – | – |
| Glb03 | No | No | – | – | – | – | – | – | – |
| Glb04 | No | No | – | – | – | – | – | – | – |
| Glb05 | No | No | – | – | – | – | – | – | – |
| Glb06 | No | No | – | – | – | – | – | – | – |
| Glb07 | No | No | – | – | – | – | – | – | – |
| Glb08 | Yes | Yes | 43 ± 2 | 75 ± 3 | 1.7 | 13 ± 4 | 17 ± 6 | 20 ± 5 | 29 ± 3 |
| Glb09 | No | No | – | – | – | – | – | – | – |
| Glb10 | No | No | – | – | – | – | – | – | – |
| Glb11 | Yes | No | – | – | – | – | – | – | – |
| Glb12 | No | No | – | – | – | – | – | – | – |
| Glb13 | No | No | – | – | – | – | – | – | – |
| Glb14 | No | Yes | 30 ± 1 | >200 | >6.7 | – | – | – | – |
| Glb15 | No | Yes | 71 ± 2 | >200 | >2.8 | 14 ± 4 | 13 ± 3 | 14 ± 6 | 12 ± 3 |
| Glb16 | Yes | Yes | 12 ± 2 | 23 ± 1 | 1.9 | – | – | – | – |
| Glb17 | No | Yes | 4 ± 1 | 58 ± 1 | 14.5 | 120 ± 20 | 100 ± 70 | Ambiguous# | Ambiguous# |
| Glb18 | No | No | – | – | – | – | – | – | – |
| Glb19 | No | No | – | – | – | – | – | – | – |
| Glb20 | No | No | – | – | – | – | – | – | – |
| Glb21 | No | No | – | – | – | – | – | – | – |
| Glb22 | No | No | – | – | – | – | – | – | – |
| Glb23 | No | Yes | >100 | 55 ± 1 | <0.5 | 26 ± 7 | 20 ± 10 | 21 ± 9 | 20 ± 30 |
| Glb24 | No | No | – | – | – | – | – | – | – |
| Glb25 | Yes | Yes | >200 | 11 ± 1 | <0.05 | 7 ± 3 | 12 ± 2 | 15 ± 9 | 14 ± 3 |
| Glb26 | No | No | – | – | – | – | – | – | – |
| Glb27 | Yes | Yes | 11 ± 1 | 13 ± 2 | 1.2 | 7 ± 1 | 7 ± 1 | 5 ± 4 | 6 ± 2 |
| Glb28 | No | Yes | – | – | – | – | – | – | – |
| GA | Yes | Yes | 0.19* | – | – | 7.6 ± 0.2** | 1.8 ± 0.3** | 1.2*** | 0.77*** |