Table 1. Antiproliferative Activity of Kobusine (1) and Derivatives 2–27a.
| cell line/IC50 (μM)a |
|||||
|---|---|---|---|---|---|
| alkaloid | A549 | MDA-MB-231 | MCF-7 | KB | KB-VIN |
| 1c | >20 | >20 | >20 | ||
| 2c | >20 | >20 | >20 | ||
| 2bc | >20 | >20 | >20 | ||
| 3c | 8.4 | 6.0 | 7.5 | ||
| 3ac | >20 | >20 | >20 | ||
| 3bc | >20 | >20 | >20 | ||
| 4 | 17.0 | 19.0 | 13.4 | 13.0 | 16.1 |
| 5 | 4.5 | 4.5 | 4.7 | 4.7 | 4.8 |
| 6c | 6.7 | 5.3 | 5.2 | ||
| 6ac | >20 | >20 | >20 | ||
| 7 | 4.4 | 4.7 | 4.2 | 4.2 | 4.6 |
| 7a | 19.5 | 21.2 | 26.9 | 19.9 | 28.9 |
| 7b | >40 | >40 | >40 | >40 | >40 |
| 8 | 4.5 | 4.6 | 5.2 | 4.6 | 5.0 |
| 8a | 7.8 | 15.9 | 18.0 | 8.9 | 11.2 |
| 9 | 19.5 | 19.9 | 18.3 | 17.4 | 19.1 |
| 9a | >40 | >40 | >40 | >40 | >40 |
| 9b | >40 | >40 | >40 | >40 | >40 |
| 10c | 6.9 | 5.3 | 5.5 | ||
| 10ac | 19.5 | 13.9 | 17.9 | ||
| 10bc | >20 | >20 | >20 | ||
| 11ac | >20 | >20 | >20 | ||
| 12ac | >20 | >20 | >20 | ||
| 13 | 4.8 | 4.5 | 4.7 | 4.6 | 4.8 |
| 13a | 18.1 | 19.3 | 19.6 | 18.1 | 20.1 |
| 14ac | 14.1 | 11.7 | 10.9 | ||
| 15c | 8.1 | 5.2 | 7.1 | ||
| 15ac | >20 | >20 | >20 | ||
| 15bc | >20 | >20 | >20 | ||
| 16 | 4.6 | 4.8 | 4.9 | 4.5 | 4.7 |
| 16a | 30.0 | 32.1 | 29.5 | 27.1 | 33.2 |
| 17 | 4.5 | 4.6 | 4.6 | 4.4 | 4.6 |
| 18 | 4.5 | 5.0 | 4.6 | 4.7 | 4.6 |
| 18a | 27.9 | 26.8 | 23.8 | 28.7 | 31.1 |
| 19 | 4.5 | 4.4 | 4.7 | 4.5 | 5.2 |
| 20 | 5.3 | 6.4 | 6.3 | 5.1 | 5.6 |
| 21 | 4.4 | 4.7 | 4.7 | 4.7 | 4.6 |
| 22 | 4.5 | 2.8 | 5.3 | 5.1 | 5.7 |
| 23 | 4.4 | 4.5 | 4.5 | 4.6 | 4.6 |
| 23a | 20.4 | 21.0 | 18.6 | 21.5 | 21.0 |
| 24 | 5.2 | 4.4 | 5.3 | 4.8 | 5.7 |
| 25 | 4.4 | 4.2 | 4.5 | 4.5 | 4.6 |
| 26c | 5.5 | 4.1 | 3.1 | ||
| 27ac | >20 | >20 | >20 | ||
| paclitaxelb | 0.0052 | 0.0067 | 0.0073 | 0.0050 | 1.3 |
a
Antiproliferative activity as IC50 values for each cell line, the concentration of the derivative that caused 50% reduction in growth relative to untreated cells as determined by the SRB assay.
b
Paclitaxel was used as an experimental control.
c
See ref (19).