Table 7.
Antagonistic potencies (IC50s) and the logarithm of the relative binding affinities (RBA) against ERα and ERβ of the newly synthesized compounds. Isoform affinity preferences and respective antagonist constants are also reported.
| Comp. | ERα a | ERβ b | logRBA c | logRBA d | Ka Erα e | Ka Erβ f |
|---|---|---|---|---|---|---|
| (IC50 nM) | (IC50 nM) | ERα | ERβ | (nM) | (nM) | |
| 3DPQ-1 | 0.57 ± 0.54 g,†,‡,§ | 74.33 ± 0.46 †,‡,§ | 2.19 ‡,§ | 0.08 †,‡,§ | 0.13 †,‡ | 41.76 †,‡,§ |
| 3DPQ-2 | 0.54 ± 0.31 †,‡,§ | 77.24 ± 0.42 †,‡,§ | 2.22 †,‡,§ | 0.06 †,‡,§ | 0.12 †,‡ | 43.39 †,‡,§ |
| 3DPQ-3 | 0.44 ± 0.31 †,‡,§ | 74.86 ± 0.14 †,‡,§ | 2.31 †,‡,§ | 0.08 †,‡,§ | 0.10 †,‡ | 42.06 †,‡,§ |
| 3DPQ-4 | 0.47 ± 0.12 †,‡,§ | 82.45 ± 0.54 †,‡,§ | 2.28 †,‡,§ | 0.03 †,‡,§ | 0.11 †,‡ | 46.32 †,‡,§ |
| 3DPQ-5 | 0.81 ± 0.43 †,‡,§ | 74.41 ± 0.46 †,‡,§ | 2.04 ‡ | 0.08 †,‡,§ | 0.18 †,‡ | 41.80 †,‡,§ |
| 3DPQ-6 | 0.84 ± 0.11 †,‡,§ | 86.56 ± 0.33 †,‡,§ | 2.03 ‡ | 0.01 †,‡,§ | 0.19 ‡ | 48.63 †,‡,§ |
| 3DPQ-7 | 0.64 ± 0.13 †,‡,§ | 72.34 ± 0.17 †,‡,§ | 2.14 †,‡ | 0.09 †,‡,§ | 0.14 †,‡ | 40.64 †,‡,§ |
| 3DPQ-8 | 0.81 ± 0.14 †,‡,§ | 72.35 ± 0.78 †,‡,§ | 2.04 ‡ | 0.09 †,‡,§ | 0.18 †,‡ | 40.65 †,‡,§ |
| 3DPQ-9 | 0.45 ± 0.14 †,‡,§ | 83.56 ± 0.46 †,‡,§ | 2.30 †,‡,§ | 0.03 †,‡,§ | 0.10 †,‡ | 46.94 †,‡,§ |
| 3DPQ-10 | 0.77 ± 0.14 †,‡,§ | 79.54 ± 0.76 †,‡,§ | 2.06 ‡ | 0.05 †,‡,§ | 0.17 †,‡ | 44.69 †,‡,§ |
| 3DPQ-11 | 0.70 ± 0.33 †,‡,§ | 76.52 ± 0.48 †,‡,§ | 2.10 ‡ | 0.07 †,‡,§ | 0.16 †,‡ | 42.99 †,‡,§ |
| 3DPQ-12 | 0.40 ± 0.43 †,‡,§ | 89.45 ± 0.31 †,‡,§ | 2.35 †,‡,§ | 0.00 †,‡,§ | 0.09 †,‡,§ | 50.25 †,‡,§ |
| E2 h | 0.88 ± 0.24 ‡,§ | 0.88 ± 0.32 ‡,§ | 2.00 | 2.00 ‡,§ | 0.20 ‡,§ | 0.49 ‡,§ |
| 4-OHT. i | 1.13 ± 0.24 †,§ | 3.62 ± 0.43 †,§ | 1.90 § | 1.39 † | 0.25 †,§ | 2.03 †,§ |
| Ral. j | 0.73 ± 0.35 †,‡ | 3.39 ± 0.16 †,‡ | 2.09 ‡ | 1.42 † | 0.16 †,‡ | 1.90 †,‡ |
| Control k | NA l | NA | NA | NA | NA | NA |
a Concentration that antagonizes the 50% of ERα signaling activity; b Concentration that antagonizes (inhibits) the 50% of ERβ signaling activity; c Logarithmic value of the percentage of relative binding affinity toward the ERα; d Logarithmic value of the percentage of relative binding affinity toward the ERβ (for both c values and d values relative binding affinity (RBA) values where calculated related to estradiol with an affinity of 100%, logRBA values higher than 0 refer to strong binders, logRBA values between −2 and 0 refer to moderate binders, logRBA values below −2 refer to weak binders); e Calculated antagonistic (i.e., inhibitory) constants against ERα; f Calculated antagonistic (i.e., inhibitory) constants against ERβ; g Results are presented as mean value ± standard deviation; h 17β-estradiol; i 4-hydroxytamoxifen; j Raloxifene; k No ligand (0.9% NaCl). l Not available. * p < 0.05 when compared with control group; † p < 0.05 when compared with E2; ‡ p < 0.05 when compared with 4-OTH; § p < 0.05 when compared with Ral.