Table 1.
Top1 inhibitory activities and unwinding effect and cytotoxicities of the synthesized compounds.
| Cpd. | Relaxation assaya | Unwinding effect | Cytotoxicity [GI50 (μM)]b
|
|||
|---|---|---|---|---|---|---|
| HL-60 | CA46 | HeLa | A549 | |||
| 1 | +++ | No | 0.30 ± 0.029 | 3.7 ± 1.4 | 22 ± 6.3 | 1.4 ± 0.30 |
| 4 | + | −c | 14 ± 1.1 | 15 ± 2.0 | 46 ± 16 | 64 ± 45 |
| 5 | + | − | 52 ± 7.6 | 13 ± 3.1 | 19 ± 4.6 | 76 ± 36 |
| 6 | + | − | 22 ± 2.2 | 13 ± 1.0 | >100 | 77 ± 6.2 |
| 7 | ++ | − | 5.7 ± 1.9 | 2.6 ± 0.88 | 62 ± 4.3 | 30 ± 1.8 |
| 8 | ++++ | Yes | 1.2 ± 0.18 | 5.9 ± 2.7 | 0.92 ± 0.034 | 0.61 ± 0.20 |
| 9 | + | − | 14 ± 4.1 | 7.9 ± 4.5 | 17 ± 2.2 | 19 ± 13 |
| 11 | ++++ | Yes | 1.2 ± 0.038 | 3.4 ± 0.0089 | 1.6 ± 0.25 | 0.89 ± 0.18 |
| 12 | ++++ | Yes | 2.8 ± 0.60 | 1.1 ± 0.17 | 1.0 ± 0.23 | 0.44 ± 0.34 |
| 13 | ++++ | Yes | 1.2 ± 0.065 | 15 ± 1.2 | 0.78 ± 0.20 | 0.49 ± 0.41 |
| 14 | ++++ | No | 2.3 ± 1.7 | 2.9 ± 1.5 | 5.8 ± 0.58 | 2.3 ± 0.33 |
| 15 | ++++ | Yes | 2.3 ± 1.8 | 1.2 ± 0.086 | 0.96 ± 0.12 | 0.37 ± 0.10 |
| 16 | ++++ | Yes | 1.4 ± 0.043 | 1.2 ± 0.063 | 1.3 ± 0.15 | 1.0 ± 0.055 |
| 17 | ++ | − | 75 ± 22 | 14 ± 0.66 | 29 ± 11 | 15 ± 2.2 |
| 18 | ++++ | Yes | 1.3 ± 0.089 | 1.2 ± 0.086 | 1.2 ± 0.18 | 3.3 ± 5.5 |
| 19 | ++++ | Yes | 1.3 ± 0.040 | 1.1 ± 0.00029 | 5.9 ± 1.2 | 4.2 ± 0.52 |
| 20 | ++++ | Yes | 2.2 ± 1.4 | 3.8 ± 1.1 | 8.9 ± 1.2 | 5.5 ± 2.1 |
| 21 | ++++ | Yes | 1.9 ± 1.1 | 2.7 ± 0.22 | 1.8 ± 0.11 | 1.2 ± 0.066 |
| 22 | +++ | No | 0.11 ± 0.0064 | 2.9 ± 0.19 | 1.1 ± 0.17 | 7.8 ± 0.89 |
| 25 | ++++ | Yes | 0.32 ± 0.070 | 3.0 ± 0.56 | 2.2 ± 0.55 | 0.52 ± 0.54 |
| 26 | ++++ | No | 0.034 ± 0.0012 | 5.8 ± 2.7 | 10 ± 0.18 | <0.01 |
| 28 | ++++ | Yes | 0.025 ± 0.0047 | 0.90 ± 0.036 | 0.48 ± 0.19 | 1.0 ± 0.025 |
| 29 | ++++ | Yes | 0.064 ± 0.0008 | 1.4 ± 0.059 | 2.2 ± 0.43 | 1.9 ± 2.3 |
| 30 | ++++ | Yes | 0.026 ± 0.0021 | 1.1 ± 0.042 | 0.94 ± 0.13 | 0.14 ± 0.15 |
| CPT | +++ | − | 0.015 ± 0.0017 | 0.52 ± 0.064 | 14 ± 4.0 | 1.6 ± 0.23 |
a
Top1 inhibitory activity was semiquantitatively expressed relative to CPT at 25 μM of tested concentration as follows: +, less than 40% of the activity; ++, between 41% and 80% of the activity; +++, between 81% and 120% of the activity; ++++, more than 121% of the activity. Every experiment was repeated at least two times independently.
b
GI50 values were defined as the concentrations of compounds that resulted in 50% cell growth inhibition, shown as means ± SD. Every experiment was repeated at least three times.
c
“−” means “not determined”.