Table 1
Side chain backbone modifications
| Compound | Inhibition of tubulin polymerization | Inhibition of colchicine binding | Inhibition of MCF-7 growth |
|---|---|---|---|
| IC50 ± SD (μm) | % inhibition ± SD | IC50 ± SD (μm) | |
| Curacin A | 0.72 ± 0.2 | 94 ± 2 | 0.038 ± 0.01 |
| Curacin B | 0.82 ± 0.2 | 56 ± 2 | 0.32 ± 0.06 |
| Curacin C | 2.3 ± 1 | 10 ± 2 (50 ± 3) | 3.6 ± 0.8 |
| 1 | 1.2 ± 0.2 | 85 ± 7 | 0.046 ± 0.01 |
| 2 | 4.6 ± 1 | 1 ± 1 (28 ± 6) | 3.3 ± 2 |
In the colchicine binding assay, inhibitor concentration was 5.0 μm, except for the values in parentheses, where the inhibitor concentration was 50 μm. Note that configuration at C13 is R in curacins B and C, as well as in curacin A. The α orientation in the diagrams of the methoxy substituent in curacins B and C is necessitated by theE-to-Z transition at the C7-8 and C9-10 olefinic bonds, respectively.
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SD, standard deviation.