Table 1.
Evaluation of 1a–g, 2a–g, 3a–g, 4a,b, 5a–c and melphalan against a panel of normal and malignant cell lines
| Compound | Human normal cells
|
Human malignant cells
|
Ave SI | log P | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| CC50a (μM)
|
HSC-2
|
HSC-4
|
HL-60
|
|||||||||
| HGF | HPC | HPLF | Ave | CC50(μM)a | SIb | CC50(μM)a | SIb | CC50(μM)a | SIb | |||
| 1a | 93 | 16 | 26 | 45 | 3.8 | 12 | 3.2 | 14 | 3.7 | 12 | 13 | 4.70 |
| 1b | 82 | 11 | 67 | 53 | 2.7 | 20 | 2.2 | 24 | 3.0 | 18 | 21 | 4.86 |
| 1c | >400 | 400 | >400 | >400 | 3.7 | >108 | 6.1 | >66 | 7.6 | >53 | >76 | 5.38 |
| 1d | >400 | >400 | >400 | >400 | >400 | ~1.0 | >400 | ~1.0 | >400 | ~1.0 | ~1.0 | 4.80 |
| 1e | >400 | >400 | >400 | >400 | 11 | >36 | 40 | >10 | 11 | >36 | >27 | 5.15 |
| 1f | >400 | >400 | 386 | >395 | 11 | >36 | 24 | >17 | 26 | >15 | >23 | 4.76 |
| 1g | 44 | 35 | 79 | 53 | 5.9 | 9.0 | 6.5 | 8.2 | 3.0 | 18 | 12 | 4.33 |
| 2a | 25 | 14 | 18 | 19 | 3.7 | 5.1 | 2.4 | 7.9 | 3.0 | 6.3 | 6.4 | 4.90 |
| 2b | 42 | 38 | 36 | 39 | 2.2 | 18 | 2.5 | 16 | 1.0 | 39 | 24 | 5.07 |
| 2c | 39 | 18 | 38 | 32 | 2.2 | 15 | 2.3 | 14 | 3.2 | 10 | 13 | 5.58 |
| 2d | >400 | >400 | >400 | >400 | 32 | >13 | 71 | >5.6 | 30 | >13 | >11 | 5.00 |
| 2e | >400 | 192 | >400 | >331 | 17 | >20 | 45 | >7.4 | 38 | >8.7 | >12 | 5.35 |
| 2f | >400 | 33 | 354 | >262 | 4.8 | >55 | 11 | >24 | 7.2 | >36 | >38 | 4.96 |
| 2g | 336 | >400 | >400 | >379 | 73 | >5.2 | 92 | >4.1 | 59 | >6.4 | >5.2 | 4.53 |
| 3a | 371 | 123 | 282 | 259 | 4.9 | 53 | 9.2 | 28 | 20 | 13 | 31 | 4.93 |
| 3b | 326 | >400 | >400 | >375 | 19 | >20 | 15 | >25 | 32 | >12 | >19 | 5.09 |
| 3cc | 191 | 345 | 332 | 289 | 1.5 | 193 | 2.7 | 107 | 4.1 | 71 | 124 | 5.60 |
| 3d | >400 | >400 | >400 | >400 | 11 | >36 | >400 | ~1.0 | >400 | ~1.0 | ~13 | 5.03 |
| 3e | >400 | 92 | 348 | >280 | 6.6 | >42 | 13 | >22 | 27 | >10 | >25 | 5.38 |
| 3fc | >400 | >400 | >400 | >400 | >400 | ~1.0 | >400 | ~1.0 | >400 | ~1.0 | ~1.0 | 4.98 |
| 3gc | 336 | 347 | 378 | 354 | 0.76 | 466 | 1.5 | 236 | 1.1 | 322 | 341 | 4.56 |
| 4a | 218 | 117 | 103 | 146 | 28 | 5.2 | 29 | 5.0 | 27 | 5.4 | 5.2 | — |
| 4b | 74 | 49 | 56 | 60 | 6.6 | 9.1 | 18 | 3.3 | 5.8 | 10 | 7.5 | — |
| 5a | >400 | >400 | >400 | >400 | >400 | ~1.0 | >400 | ~1.0 | >400 | ~1.0 | ~1.0 | — |
| 5b | >400 | >400 | >400 | >400 | 67 | >6.0 | 250 | >1.6 | 400 | ~1.0 | ~2.9 | — |
| 5c | >400 | >400 | >400 | >400 | >400 | ~1.0 | >400 | ~1.0 | 11 | >36 | ~13 | — |
| Melphaland | >200 | >200 | >200 | >200 | 35 | >5.7 | 81 | >2.5 | 6.0 | >33 | >14 | — |
The CC50 value is the concentration of the compound which reduces the number of viable cells by 50% and was obtained from duplicate determinations. The differences between the CC50 figures in the two bioassays are less than 5%. The maximum concentration of each compound was 400 μM except solubility considerations necessitated the highest concentration of melphalan to be 200 μM.
The letters SI indicate the selectivity index and is the quotient of the average CC50 figure of the three normal cells and the CC50 value of a malignant cell line.
With the exception of the result using HSC-4 cells, the data were reported previously26 [copyright (2005) by Elsevier].
The data were reported previously27 [copyright (2008) by Elsevier].