Table 2.
Summary of enones 1 and 4a–e and allylic alcohols 5b–e: Yield, IC50 values of the inhibition between coregulatory peptide SRC2-2 and TRα/TRβ, viability (LD50) of U2OS and ARO cells in the presence of compound, solubility in PBS buffer containing 5% DMSO, and permeability across an artificial membrane (PAMPA).
| In vitro Potency | Cytotoxicity | Pharmacological Properties | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Entry | R1 = 4-hexylbenzene and R = 4-heptylbenzene | Compound | Yielda5 (%) | Yielda4 (%) | TRαb IC50 (μM) | TRβb IC50 (μM) | TRα: TRβ ratio | AROc LD50 (μM) | U2OSc LD50 (μM) | Solubilityc (μM) | Permeabilityc (10−6 cm/s) |
| 1 |
|
1 | - | 55 | 28.1 | 1.5 | 18.7 | 4.5 | 10.1 | 36 | 38 |
| 2 |
|
4a | - | 45 | 19.2 | 17.7 | 1.1 | 5.5 | 57.4 | 252 | 66 |
| 3 |
|
4b | 67 | 57 | 18.9 | 7.6 | 2.5 | 1.4 | 11.6 | 41 | 7 |
| 4 |
|
4c | 67 | 67 | 52.9 | 23.2 | 2.3 | 10.7 | 18.7 | 37 | 43 |
| 5 |
|
4d | 51 | 64 | >100 | >100 | - | >200 | >200 | 24 | 0 |
| 6 |
|
4e | 46 | 59 | >100 | >100 | - | >200 | >200 | 36 | 0 |
| 7 |
|
4f | 54 | 77 | >100 | >100 | - | >200 | 57.0 | 30 | 0 |
| 8 |
|
4g | - | 85 | >100 | >100 | - | >200 | >200 | 14 | 0 |
a
Isolated yield;
b
values are means of two independent experiments done in quadruplicate; the general error limits are 10%;
c
values are means of two independent experiments done in triplicate; the general error limits are 10–15%. Actual error values for each measurement are omitted for clarity but are included in tables in the supplemental materials.