Table 1.
| Compound | ED50 (μM)a | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| R | R′ | X | A549 | HCT-8 | MCF-7 | 1A9 | PC-3 | HepG2 | KB | KB-V | |
| 1 | Me | Me | H | 11.2 | 11.8 | NTb | 11.2 | 35.6 | NT | 12.8 | 9.6 |
| 2 | Pr | Me | H | 3.6 | 3.5 | NT | 3.7 | 8.2 | NT | 4.6 | 3.4 |
| 3 | Pr | Me | Br | 2.0 | 2.6 | NT | 1.9 | 4.7 | NT | 1.8 | 1.8 |
| 21 | Bu | Me | H | 6.4 | 7.8 | 4.4 | 5.9 | 13.0 | 23.9 | 7.0 | 8.6 |
| 22 | iBu | Me | H | 4.4 | 7.5 | 3.7 | 8.0 | 12.4 | 14.5 | 7.9 | 8.2 |
| 23 | iPen | Me | H | 18.4 | 13.0 | 25.2 | 16.3 | NAc | NA | 17.5 | 20.3 |
| 24 | Prenyl | Me | H | 10.3 | 13.7 | 8.2 | NT | 12.2 | 11.2 | 13.3 | 8.9 |
| 25 | Pr | Et | H | 4.6 | 5.6 | 2.6 | 4.3 | 12.5 | 11.2 | 6.4 | 3.5 |
| 26 | Pr | Pr | H | 1.9 | 2.6 | 1.6 | 2.0 | 8.6 | 8.3 | 2.7 | 2.4 |
| 27 | Pr | Bu | H | 7.1 | 8.7 | 5.3 | NT | 9.6 | 8.0 | 8.0 | 8.9 |
| 28 | Pr | iBu | H | 1.7 | 8.0 | 4.4 | 6.9 | 12.2 | 13.4 | 4.8 | 4.1 |
| 29 | Pr | iPen | H | 11.3 | 15.3 | 9.1 | NT | 17.0 | 15.5 | 10.6 | 19.2 |
| 30 | – | – | – | 7.1 | 6.7 | 5.8 | NT | 8.4 | 6.4 | 8.2 | 7.3 |
| 31 | Pr | Me | I | 1.4 | 1.1 | 1.8 | 1.8 | 2.8 | 2.4 | 1.5 | 1.4 |
| 32 | Pr | Pr | I | 8.2 | 7.8 | 5.1 | NT | 9.6 | 7.3 | 6.4 | 6.2 |
| Paclitaxel (nM) | 2.56 | >100 | >100 | 2.09 | 8.87 | >100 | 2.87 | >100 | |||
| Vincristine (nM) | 4.8 | 24.2 | 12.1 | NT | 12.1 | 2.9 | 2.4 | >100 | |||
a
Antiproliferative activity as ED50 values for each cell line, the concentration of compound that caused 50% reduction in absorbance at 562 nm relative to untreated cells using the sulforhodamine B assay. Human lung carcinoma (A549), colon adenocarcinoma (HCT-8), breast cancer (MCF-7), ovarian carcinoma (1A9), prostate cancer (PC-3), liver cancer (HepG2), epidermoid carcinoma of the nasopharynx (KB), and MDR expressing P-glycoprotein (KB-VIN).
b
NT, not tested.
c
NA, not active.
Test compound (20 μg/mL) did not reach 50% inhibition.