Table 3.
Chemical Structure, Growth Inhibition of MDA-MB-231 Breast Tumor Cell Line, and PDE5 Inhibitory Activity of 1,2,3-Trisubstituted-tetrahydro-β-carbolines (31–40)
| compd | stereochemistry | X,Y | % growth inhibition at 10 μMa | growth inhibition IC50 (μM) and CI at p < 0.05b | % PDE 5 inhibition at 10 μMa | PDE 5 inhibition IC50 (μM) and CI at p < 0.05b |
|---|---|---|---|---|---|---|
| 31 | 1R,3R | 2,4-dichloro | 98 | 0.56 (0.52–0.61) | 66 | 2.30 (1.71–3.08) |
| 32 | 1S,3R | 2,4-dichloro | 98 | 0.07 (0.05–0.11) | 25 | ND |
| 33 | 1S,3S | 2,4-dichloro | 55 | ND | 99 | 0.38 (0.25–0.44) |
| 34 | 1R,3S | 2,4-dichloro | 98 | 1.24 (1.05–1.48) | 38 | ND |
| 35 | 1R,3R | 3,4-dichloro | 40 | ND | 40 | ND |
| 36 | 1S,3R | 3,4-dichloro | 50 | ND | 30 | ND |
| 37 | 1S,3S | 3,4-dichloro | 43 | ND | 20 | ND |
| 38 | 1R,3S | 3,4-dichloro | 55 | ND | 40 | ND |
| 39 | 1R,3R | 2,6-dichloro | 15 | ND | 27 | ND |
| 40 | 1S,3S | 2,6-dichloro | 30 | ND | 67 | 0.73 (0.64–0.83) |
a
Calculated from duplicate values.
b
Calculated from at least 8 concentrations, each with quadruple replicates, p < 0.05.