Table 1.
Inhibition of the AKR1C enzymes by the halogenated oestrone derivatives.
| AKR1C1 |
AKR1C2 |
AKR1C3 |
|||||||
|---|---|---|---|---|---|---|---|---|---|
| Inhibition (%) |
IC50/Ki (μM) | Inhibition (%) |
IC50/Ki (μM) | Inhibition (%) |
IC50/Ki (μM) | ||||
| Compound | 100 μM | 10 μM | 100 μM | 10 μM | 100 μM | 10 μM | |||
| 1 | 10.0 | NI | 50.0 | NI | NI | NI | |||
| 1Me | 22.5 | 8.2 | 70.0 | 4.8 | NI | 16.7 | |||
| 1_2I | 22.5 | 31.3 | 52.5 | 20.2 | NI | NI | |||
| 1_4I | 10.0 | 8.3 | NI | NI | NI | 36.4 | |||
| 1_2I,4I | 25.0 | 42.2 | 62.2 | 21.3 | NI | 13.6 | |||
| 1_2Br | 65.0 | 51.2 | 25.0 | 36.4 | 40.2 | 13.0 | |||
| 1_4Br | 100.0 | NI | 62.5 | 73.0 | 7.0 | 8.3 | 25.0 | ||
| 1_2Br,4Br | 82.5 | 67.0 | 5.4 | 99.8 | 83.0 | 5.6 | 58.3 | 50.0 | |
| 1_2Cl | 91.6 | 50.0 | 88.0 | 53.0 | 86.8 | NI | |||
| 1_4Cl | 80.0 | NI | 25.0 | 70.0 | 5.3 | 91.7 | 50.0 | ||
| 1_2Cl,4Cl | 94.8 | 46.9 | 1.6/0.69 | 50.0 | 23.4 | 90.4 | 21.9 | 6.3, 1.43 | |
| 2 | 22.5 | 7.5 | 65.0 | 3.5 | 29.8 | 22.5 | |||
| 2Me | 20.0 | 1.3 | 35.0 | NI | 59.9 | 22.9 | |||
| 2_2I | 42.5 | 37.8 | 50.0 | 22.4 | NI | 33.8 | |||
| 2_4I | 22.5 | 2.3 | 75.0 | 16.5 | 85.7 | 35.1 | 12.3 | ||
| 2_2I,4I | 77.5 | NI | 45.0 | NI | 50.0 | 2.6 | |||
| 2_2Br | 22.5 | 47.2 | 65.0 | 81.4 | 1.5 | 23.8 | 62.6 | ||
| 2_4Br | 14.2 | NI | 98.3 | 80.0 | 2.2 | 58.2 | 25.0 | ||
| 2_2Br,4Br | 88.7 | 82.5 | 5.3 | 86.0 | 70.3 | 7.3 | 50.8 | 27.9 | |
| 2_2Cl | 45.1 | 50.0 | 75.4 | 83.0 | 2.1 | 72.3 | 60.0 | 8.7 | |
| 2_4Cl | 22.5 | 18.5 | 80.0 | 73.9 | 1.8 | 43.6 | 5.3 | ||
| 2_2Cl,4Cl | 95.9 | 84.8 | 2.8 | 81.5 | 84.1 | 4.6 | 89.8 | 69.9 | 12.8 |
| 2_2I,4Br | 93.4 | 90.7 | 0.7/0.57 | 74.7 | 59.5 | 43.6 | 40.0 | ||
| 2_2I,4Cl | 99 | 90.0 | 0.8 | 87.5 | 73.0 | 7.1 | 72.2 | 50.0 | |
| 2_2Br,4I | 100 | 67.0 | 7.2 | 100 | 75.0 | 4.4 | 88.9 | 50.0 | |
| 2_2Br,4Cl | 92.3 | 80.0 | 1.7 | 99.0 | 80.0 | 3.1 | 89.4 | 50.0 | |
| 2_2Cl,4I | 82.6 | 50.0 | 89.2 | 73.0 | 4.6 | 58.0 | NI | ||
| 2_2Cl,4Br | 93.9 | 80.0 | 1.9 | 91.9 | 65.0 | 88.0 | 25.0 | ||
| 2Me_2Br | NI | 7.1 | NI | NI | 18.3 | 13.6 | |||
| 2Me_4Br | 12.5 | 12.9 | 15.0 | NI | 39.7 | 44.6 | |||
| 2Me_2I | NI | 1.0 | 5.0 | NI | 50.8 | NI | |||
| 2Me_4I | NI | 5.1 | NI | NI | 19.8 | NI | |||
| 2Me_2Cl | 35.7 | 17.0 | 76.3 | 60.0 | 91.0 | 60.0 | |||
| 2Me_4Cl | 21.4 | NI | 78.8 | 50.0 | 90.0 | 50.0 | |||
| 3 | 12.5 | 13.8 | NI | NI | NI | 23.4 | |||
| 3Me | NI | NI | 75.0 | NI | 49.2 | 21.1 | |||
| 3_2Cl,4Cl | 2.8 | 39.4 | 76.8 | 66.2 | 44.6 | NI | |||
| 3_2Br,4Br | 64.3 | 33.0 | 74.4 | 68.0 | 0.9/1.98 | 26.7 | 50.0 | ||
| 3_2I,4I | 9.8 | 17.5 | 11.7 | 22.9 | 27.3 | 11.4 | |||
| 4 | 25.0 | NI | 30.0 | NI | NI | NI | |||
| 5 | 50.0 | 7.1 | 75.0 | 10.5 | 41.7 | 24.1 | |||
NI: no inhibition.
Data in bold, compounds showing ≥80% inhibition for the respective AKR1C.