Table 1.
In vitro growth inhibitory effects (μM) of UC-112 analogs with modification of benzyloxy moiety.
| |||||||
|---|---|---|---|---|---|---|---|
| compound | R | A375 | WM164 | RPMI7951 | M14 | M14/MDR1 | RIb |
| 2a |
|
3.6±0.2 | 8.6±1.1 | 11.1±0.7 | 5.4±0.3 | 7.0±0.1 | 1.3 |
| 2b |
|
1.9±0.1 | >30.0 | 6.5±0.2 | 2.3±0.1 | 3.1±0.1 | 1.3 |
| 2c |
|
3.9±0.1 | 56.4±1.1 | 17.4±1.2 | 4.1±0.2 | 7.9±0.1 | 1.9 |
| 2d |
|
14.1±0.7 | 33.9±1.1 | 21.0±0.4 | 11.5±0.4 | 14.3±0.2 | 1.2 |
| 6a |
|
>30.0 | 13.0 ±0.5 | >30.0 | >30.0 | >30.0 | NDa |
| 6b |
|
4.7 ±0.2 | 3.7 ±0.3 | 26.2±6.2 | 5.1±0.1 | 10.7±1.2 | 2.1 |
| 6c |
|
3.5 ±0.3 | 2.8 ±0.2 | 18.4±0.3 | 8.6±0.2 | 7.4±1.2 | 0.9 |
| 6d |
|
1.5 ±0.1 | 1.6 ±0.1 | 12.9±0.2 | >30.0 | 12.2±0.2 | ND |
| 6e |
|
6.0±1.3 | 24.9 ± 1.0 | 25.3±2.4 | 6.7±0.3 | 12.2±0.5 | 1.8 |
| 6f |
|
2.9±0.15 | ND | 6.8±0.6 | 2.4±0.1 | 3.3±0.2 | 1.4 |
| 8 |
|
>30.0 | 20.18±0.49 | 17.3±0.3 | >30.0 | 8.7±0.2 | ND |
| 10a |
|
0.8 ±0.1 | 0.9 ±0.1 | 4.4±0.3 | 0.8 ±0.1 | 2.1±0.1 | 2.6 |
| UC-112 |
|
1.9 ±0.6 | ND | ND | 2.1 ±0.4 | 3.2 ±0.5 | 1.5 |
| MX-106 |
|
0.9 ±0.1 | 1.1 ±0.2 | ND | 0.8 ±0.2 | 1.8 ±0.4 | 2.3 |
a
ND: Not Determined.
b
Resistance index (RI) is calculated by dividing IC50 values on multidrug-resistant cell line M14/MDR1 by IC50 values on the matching sensitive parental cell line M14.