Table 1.
Six compounds (B1, B2, B4, C6, D3, D6, and CUR) were selected for determining the IC50 values of IKKβ kinase activity, and the active compounds B1, B2, B4, and D6 (IKKβ IC50 <10 μM) were further measured for the antiproliferative effects in three PC cell lines (PANC-1, MiaPaCa-2, and BxPC-3) by the well-established MTT assay
| Compound | IC50 (µM)
|
|||
|---|---|---|---|---|
| IKKβ | PANC-1 | MiaPaCa-2 | BxPC-3 | |
| B1 | 8.9±1.1 | 12.8±6.9 | 11.8±1.8 | 21.5±13.3 |
| B2 | 5.6±0.5 | 9.6±2.7 | 10.6±4.3 | 12.0±0.9 |
| B4 | 3.4±1.4 | 8.2±0.9 | 6.3±1.3 | 5.2±1.1 |
| C6 | 12.4±5.6 | NDa | NDa | NDa |
| D3 | >20 | NDa | NDa | NDa |
| D6 | 0.8±0.3 | 0.7±1.1 | 1.3±0.4 | 1.9±1.3 |
| EF31 | 1.92b | 1.7±1.8 | 5.0±0.5 | 2.1±0.9 |
| EF24 | 1.9b | 2.8±3.0 | 4.2±1.5 | 5.9±5.9 |
| CUR | 20.5±1.5 | 21.5±17.3 | 24.8±7.4 | 17.9±2.3 |
Notes: The test results at both enzyme and cell levels are shown. The lead compounds EF31, EF24, and CUR are used for comparison. 1.92a and 1.9a were the IC50 values of EF31 and EF24, respectively, against IKKβ.31,32 All data are presented as the mean value of three to five independent tests. NDa means not determined; 1.92b and 1.9b are the IC50 values in the previous reported reference. The bold values represent the favorable inhibitory activity of two most active derivatives of EF24 and EF31.
Abbreviations: CUR, curcumin; IC50, half-maximal inhibitory concentration; IKKβ, inhibitory kappa B kinase β; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; ND, not determined.