Table 4:
Activity of selected modified carbazole with tubulin and microtubules. Colchicine binding to tubulin and tubulin assembly (as assessed by turbidity development of tubulin solutions) were inhibited in a dose dependent manner by combretastatin A-4 (1) and nocodazole (3) (positive controls) and by the selected modified carbazoles. Results are the mean ± standard deviation (SD) of at least three independent experiments. MT and free tubulin partitioning was shifted toward free tubulin by all compounds indicating MT destabilization. EC50 values are the results from representative experiments that were repeated three times with comparable results. Not determined (ND).
| Compounds | Colchicine Binding | Tubulin Assembly | MT-Tubulin Partitioning | |
|---|---|---|---|---|
| % Inhibition | IC50 (μM) | EC50 (μM) | ||
| mean ± SD | mean ± SD | mean | ||
| at 5 μM | at 1 μM | |||
| 1 | 98 ± 0.1 | 89 ± 3 | 0.64 ± 0.01 | 0.6 |
| 3 | 74 ± 0.8 | 23 ± 0.8 | 0.48 ± 0.01 | 2.4 |
| 23 | 4 ± 1 | ND | > 20 | > 20 |
| 25 | 41 ± 4 | ND | 4.4 ± 0.4 | 5.3 |
| 8 | 53 ± 3 | ND | 1.4 ± 0.2 | 2.1 |
| 27 | 70 ± 1 | ND | 1.6 ± 0.01 | 6.4 |
| 20 | 91 ± 1 | 61 ± 4 | 0.89 ± 0.04 | 3.4 |