Table 1.
Cytotoxicity of compounds 1–6 in the presence or absence of Akt inhibitorsa.
| Compoundsb | GI50 (μM)c |
|||
|---|---|---|---|---|
| MDA-MB468d | MDA-MB231d | MCF7d | 184B5d | |
| 1e | 28.58 ± 1.25 | 22.52 ± 1.44 | 38.44 ± 1.20 | 76.13 ± 1.13 |
| 1f | 6.53 ± 0.14 | 8.33 ± 0.25 | 7.54 ± 0.17 | >20 |
| 1g | 6.83 ± 0.18 | 12.59 ± 0.29 | 5.51 ± 0.13 | >20 |
| 1h | 2.81 ± 0.12 | 6.08 ± 0.16 | 11.78 ± 0.21 | >20 |
| 1i | 9.14 ± 0.25 | 18.82 ± 0.28 | 7.71 ± 0.18 | >20 |
| 2e | 6.02 ± 0.13 | 15.87 ± 0.75 | 8.45 ± 0.18 | 18.35 ± 0.75 |
| 2f | 3.95 ± 0.09 | 12.31 ± 0.31 | 10.20 ± 0.15 | >20 |
| 2g | 7.09 ± 0.19 | 8.80 ± 0.24 | 5.60 ± 0.08 | 16.64 ± 0.56 |
| 2h | 4.30 ± 0.09 | 6.50 ± 0.15 | 11.40 ± 0.23 | 19.45 ± 0.81 |
| 2i | 7.42 ± 0.21 | 11.33 ± 0.24 | 9.55 ± 0.19 | >20 |
| 3e | 1.41 ± 0.09 | 6.32 ± 0.15 | 1.98 ± 0.10 | 18.65 ± 0.82 |
| 3f | 2.69 ± 0.08 | 7.25 ± 0.14 | 5.78 ± 0.15 | 12.38 ± 0.21 |
| 3g | 2.09 ± 0.07 | 5.63 ± 0.12 | 1.63 ± 0.05 | 14.93 ± 0.62 |
| 3h | 1.44 ± 0.05 | 3.74 ± 0.08 | 3.70 ± 0.06 | 8.19 ± 0.19 |
| 3i | 3.50 ± 0.09 | 12.31 ± 0.21 | 3.17 ± 0.09 | 12.45 ± 0.2 |
| 4e | 13.29 ± 0.61 | 8.59 ± 0.16 | 15.36 ± 0.72 | 44.48 ± 1.01 |
| 4f | 3.43 ± 0.08 | 5.66 ± 0.18 | 4.96 ± 0.09 | >20 |
| 4g | 6.50 ± 0.16 | 2.87 ± 0.17 | 3.32 ± 0.08 | >20 |
| 4h | 3.24 ± 0.09 | 0.74 ± 0.11 | 7.37 ± 0.26 | >20 |
| 4i | 19.27 ± 0.21 | 9.88 ± 0.16 | 7.54 ± 0.22 | >20 |
| 5e | 8.73 ± 0.17 | 7.08 ± 0.18 | 3.42 ± 0.13 | 40.36 ± 0.92 |
| 5f | 4.87 ± 0.08 | 2.50 ± 0.09 | 2.56 ± 0.05 | >20 |
| 5g | 4.95 ± 0.10 | 1.94 ± 0.05 | 1.73 ± 0.04 | >20 |
| 5h | 4.61 ± 0.09 | 2.00 ± 0.10 | 3.26 ± 0.09 | >20 |
| 5i | 7.62 ± 0.19 | 9.45 ± 0.16 | 2.64 ± 0.07 | >20 |
| 6e | 4.80 ± 0.12 | 4.50 ± 0.11 | 3.89 ± 0.16 | 44.60 ± 0.99 |
| 6f | 5.85 ± 0.17 | 4.49 ± 0.13 | 3.54 ± 0.08 | >20 |
| 6g | 5.91 ± 0.18 | 0.74 ± 0.11 | 1.82 ± 0.05 | >20 |
| 6h | 5.66 ± 0.19 | 1.24 ± 0.09 | 3.66 ± 0.09 | >20 |
| 6i | 7.62 ± 0.22 | 9.45 ± 0.21 | 2.65 ± 0.06 | >20 |
Calculation was from sigmoidal dose response curves (variable slope) that were generated using GraphPad Prism V. 4.02 (GraphPad Software Inc.).
The structures of compounds are shown in Fig. 1.
GI50, concentration of drug required to reduce cell proliferation to 50% of the untreated control; values are mean of triplicates of at least three independent experiments.
Human breast cancer cell lines or immortalized breast cell line (184B5).
Used CQ or CQ analog only.
Used CQ or CQ analog in combination with 0.04 μM compound 7.
Used CQ or CQ analog in combination with 0.4 μM compound 8.
Used CQ or CQ analog in combination with 3.5 μM compound 9.
Used CQ or CQ analog in combination with 0.5 μM compound 10. Some of the GI50 on 184B5 cells are expressed only as “>20” because only a few dilutions were used for experiments in generating dose response curves.