Table 1.
Structures of compounds considered in this study, along with IC50 values determined against the parental KB-3-1 cell line, and the P-glycoprotein expressing cell line KB-V1. The MDR1 selectivity is calculated as the ratio of a compound’s IC50 against KB-3-1 cells divided by its IC50 against KB-V1 cells. A value > 1 indicates that the compound kills P-gp-expressing cells more effectively than parental cells, so-called MDR1-selective activity. A value < 1 indicates that the P-gp expressing cells are resistant to the compound, relative to parental cells, as is normally observed for P-gp substrates. ‘n/a’ denotes compounds, as described in the discussion, that were not tested for their biological activity as they were shown to have been incorrectly identified or impure.
| Compound | IC50, KB 3–1 (μM) | IC50, KB–V1 (μM) | MDR1 selectivitya |
|---|---|---|---|
 1 |
14.2 ± 2.1 | 3.3 ± 1.3 | 4.3 |
 2 |
n/a | n/a | n/a |
 3 |
17.0 ± 6.6 | 34.3 ± 14.2 | 0.5 |
 4 |
14.5 ± 8.1 | 10.2 ± 2.1 | 1.4 |
 5 |
n/a | n/a | n/a |
 6 |
13.1 ± 4.8 | 5.8 ± 2.5 | 2.3 |
 7 |
28.4 ± 5.2 | 4.0 ± 0.6 | 7.1 |
 8 |
>50 | >50 | - |
 9 |
1.4 ± 2.5 | 5.9 ± 2.6 | 0.2 |
 10 |
1.9 ± 0.8 | 2.1 ± 0.3 | 0.9 |
 11 |
>50 | >50 | - |
 12 |
>50 | >50 | - |
 13 |
>50 | >50 | - |
 14 |
>50 | >50 | - |
 15 |
>50 | >50 | - |
 16 |
>50 | >50 | - |
 17 |
n/a | n/a | n/a |
 18 |
39.3 ± 23.3 | 5.2 ± 1.1 | 7.5 |
 19 |
19.6 ± 1.7 | 9.3 ± 2.8 | 2.1 |
 20 |
>50 | >50 | - |
 21 |
3.4 ± 1.5 | 2.4 ± 0.5 | 1.4 |
 22 |
4.4 ± 3.6 | 30.3 ± 5.9 | 0.1 |
 23 |
26.3 ± 5.5 | 6.7 ± 2.9 | 4.0 |
 24 |
26.1 ± 2.6 | 20.7 ± 7.7 | 1.3 |
 25 |
27.7 ± 3.3 | >50 | - |
 26 |
>50 | >50 | - |