Table 3.
Evaluation of anti-proliferative activity of α-amanitin and α-amanitin conjugates 7–11 in U-87, MDA-MB-468 and A549.
| entry | structure (name) | IC50 (nM)a | ||
| U87 (αVβ3+) | MDA-MB-468 (αVβ3−) | A549 (αVβ3−) | ||
| 1 | α-amanitin | 347 ± 132.5b | 185 ± 49.6b | 518 ± 305b |
| 2 | cyclo[DKP-RGD]-uncleavable-α-amanitin (7) | 2552 ± 37.6 | 1111 ± 228.4 | n.d.c |
| 3 | cyclo[DKP-isoDGR]-uncleavable-α-amanitin (8) | 3355 ± 19.1 | 2200 ± 96.2 | n.d.c |
| 4 | cyclo[DKP-RGD]-Val-Ala-α-amanitin (9) | 1446 ± 83.9 | 202 ± 10.3 | 2160 ± 23.3 |
| 5 | cyclo[DKP-isoDGR]-Val-Ala-α-amanitin (10) | 143 ± 33.8 | 59 ± 23.4 | 217 ± 98.3 |
| 6 | cyclo[DKP-isoDGR]-PEG-4-Val-Ala-α-amanitin (11) | 165 ± 4.0 | 66 ± 24.1 | 720 ± 98.1 |
aIC50 values were calculated as the concentration of compound required for 50% inhibition of cell viability. All cell lines were treated with different concentrations of α-amanitin and compounds 7–11 for 96 hours. The samples were measured in triplicate. bAverage values from three independent experiments. cn.d.: these data could not be determined.