Table 3.
In vitro inhibitory activities of compounds 1–10 towards targets of the DHC biological space, expressed as percent inhibition (0–100%) at 10-µM compound concentration relative to the DMSO mock control. Shown is the mean of three independent experiments (n = 3) plus/minus the standard deviation. Different compounds were used as positive controls (PC), as indicated in the Materials and Methods. Highly negative values of 17β HSD2 assays are believed to be technical artefacts, as enzyme activation seems unlikely.
| Compound | Aromatase | 17β HSD2 | 17β HSD3 | AKR1C3 | 5-LO | COX-1 |
|---|---|---|---|---|---|---|
| 1 | 13.8 ± 2.0 | −50.7 ± 22.7 | 1.7 ± 4.5 | 24.8 ± 5.9 | 85.4 ± 9.3 | 43.5 ± 7.2 |
| 2 | 21.1 ± 11.7 | −14.1 ± 27.1 | 43.8 ± 4.7 | 15.5 ± 4.9 | 99.2 ± 1.2 | 48.1 ± 12.0 |
| 3 | −1.0 ± 12.0 | −26.3 ± 28.8 | −28.0 ± 20.5 | 13.8 ± 10.0 | 54.1 ± 11.6 | 53.9 ± 5.3 |
| 4 | 3.5 ± 19.0 | −31.2 ± 8.1 | 52.7 ± 49.6 | 34.4 ± 5.1 | 39.2 ± 11.1 | 24.4 ± 4.2 |
| 5 | 17.0 ± 2.0 | −17.6 ± 39.0 | 32.1 ± 27.2 | 35.2 ± 3.8 | 47.2 ± 24.2 | 49.5 ± 1.9 |
| 6 | 13.8 ± 4.4 | −39 ± 29.9 | 16.7 ± 14.5 | −6.1 ± 6.8 | 34.8 ± 14.2 | 12.34 ± 29.0 |
| 7 | 9.4 ± 3.5 | −40.5 ± 22.9 | 20.2 ± 17.7 | −7.2 ± 8.9 | 40.8 ± 4.1 | −4.2 ± 45.6 |
| 8 | 5.9 ± 3.5 | −49.8 ± 21.4 | −0.6 ± 10.0 | 5.3 ± 11.5 | 45.5 ± 2.7 | 15.3 ± 26.4 |
| 9 | 0.67 ± 4.0 | −37.1 ± 44.3 | 45.8 ± 14.2 | −1.3 ± 1.9 | 31.8 ± 29.4 | −11.4 ± 15.1 |
| 10 | 0 ± 5.8 | −32.2 ± 15.4 | 37.5 ± 23.9 | 7.4 ± 11.8 | 7.7 ± 6.0 | 11.1 ± 13.2 |
| PC | 70.2 ± 0.5 * | 76.1 ± 11.4 † | 101.2 ± 2.4 ‡ | 90.5 ± 1.2 § | 79.26 ± 5.95 ¶ | 81.3 ± 7.5 # |
* 10-nM anastrozole (CAS: 120511-73-1). † 1-µM ML376 (CAS: 1340482-23-6). ‡ 1-µM compound 24 (CAS: 873206-61-2) [34]. § 1-µM compound 2–9 (CAS: 745028-76-6) [35]. ¶ 3-µM zileuton (CAS: 111406-87-2). # 10-µM indomethacin (CAS: 53-86-1) (see Supplementary Information S-5).