Table 1.
Evaluation of 5, 5′ substituted compound 2 derivatives using a combination of 1D 1H-NMR binding assays and cell viability assays
 |
EC50 (μM) | ||||||
|---|---|---|---|---|---|---|---|
| Compound | R = | 1D-1H NMRa* | RS11846c* | H1299b* | H460b* | PC3MLb* | BP3c* |
| 1 | +++ | 4.2 | 6.0 | 3.0 | 3.1 | 1.42 | |
| 2 |  |
++ | 5.0 | 3.4 | 3.5 | 10.4 | 4.7 |
| 14 |  |
− | >30 | >30 | >30 | >30 | >30 |
| 8a |  |
+ | 15.1 | 8.0 | 3.5 | 15.1 | NDd* |
| 8b |  |
+ | 13.7 | 8.0 | 8.5 | 12.2 | ND |
| 8c |  |
+ | 10.8 | 17.0 | 10.1 | 8.5 | ND |
| 8d |  |
+ | 4.7 | 5.0 | 4.1 | 8.3 | ND |
| 8e |  |
+ | 12.6 | 28.7 | 16.7 | 12.2 | ND |
| 8f |  |
+++ | 4.2 | ND | 1.5 | ND | ND |
| 8g |  |
+ | 9.3 | 3.6 | 4.6 | 13.7 | ND |
| 8h |  |
+++ | 4.8 | 3.1 | 2.9 | 10.2 | ND |
| 8i |  |
+++ | 7.3 | 5.2 | 3.3 | 8.3 | ND |
| 8j |  |
++ | 3.0 | 3.6 | 1.4 | 0.7 | 1.5 |
| 8k |  |
+++ | 5.5 | 3.2 | 0.50 | 5.0 | 1.5 |
| 8l |  |
+ | >10 | ND | ND | ND | ND |
| 8m |  |
+++ | 4.9 | 4.8 | 0.41 | 3.7 | 0.90 |
| 8n |  |
++ | 3.1 | 3.6 | 0.55 | 3.9 | 0.72 |
| 8o |  |
+ | 5.6 | ND | 0.70 | ND | ND |
| 8p |  |
+++ | 4.6 | 7.8 | 0.99 | 3.2 | 0.41 |
| 8q |  |
+++ | 3.0 | 0.36 | 0.40 | 1.7 | 0.2 |
| 8r |  |
++ | 5.8 | 3.2 | 0.33 | 1.7 | 0.66 |
| 8s |  |
++ | 4.1 | 7.1 | 0.94 | 3.0 | 1.1 |
| 8t |  |
++ | 5.1 | ND | 1.3 | ND | 0.70 |
a*
4-point-rating scale: +++, Very Active; ++, Active; +, Mild; −, Weak
b*
Compounds against cell line using ATP-LITE assay
c*
Compounds against cell line using Annexin V-FITC and propidium iodide assay
d*
ND: not determined