Table 2.
Cytotoxicity of pyrazole (celecoxib analogs), isoxazole, pyrazolone, and positive control compounds P1–P25 (structures, Figure 3) against cells of human cutaneous melanoma and non-melanoma skin cancer lines relative to standard control noncancerous immortalised HaCaT cells.
| Compd. ID | Cell lines, IC50 values in μM, and selectivity index (SI) |
||||
|---|---|---|---|---|---|
| Melanoma |
Non-melanoma |
Control |
|||
| A375 | SKMEL-28 | GFP-A431 | SCC-12 | HaCaT | |
| P1 | 47.7 ± 4.2 | 42.8 ± 0.3 | 41.6 ± 0.8 | 257.3 ± 18.4 | 60.5 ± 3.9 |
| P2 | 54.3 ± 1.6 | 42.6 ± 1.5 | 43.9 ± 2.1 | 245.6 ± 37.3 | 44.2 ± 1.1 |
| P3 | 54.8 ± 2.7 | 59.1 ± 4.6 | 27.2 ± 0.9 (1.6) | 546.5 ± 20.7 (0.1) | 42.1 ± 3.4 |
| P4 | 58.4 ± 4.5 | 62.3 ± 2.7 | 70.8 ± 6.2 | 215.8 ± 13.4 | 76.1 ± 0.0 |
| P5 | 65.3 ± 4.2 | 130.9 ± 2.4 | 42.1 ± 3.1 (6.3) | 77.6 ± 1.7 (3.4) | 265.4 ± 4.3 |
| P6 | 113.5 ± 3.3 | 47.4 ± 1.2 | 69.8 ± 7.5 (2.1) | 49.9 ± 3.4 (3.0) | 147.2 ± 0.8 |
| P7 | 53.3 ± 4.2 | 46.0 ± 1.0 | 47.8 ± 2.0 | 43.0 ± 2.1 | 59.2 ± 3.5 |
| P8 | 55.3 ± 3.8 | 180.9 ± 4.7 | 72.2 ± 5.2 | 120.0 ± 8.5 | 44.5 ± 1.4 |
| P9 | 45.2 ± 2.0 | 40.8 ± 1.0 | 28.0 ± 3.6 (1.6) | 28.8 ± 1.4 (1.5) | 43.6 ± 1.4 |
| P10 | 55.3 ± 2.5 | 43.7 ± 2.7 | 195.5 ± 3.8 | 49.1 ± 2.0 | 68.0 ± 1.2 |
| P11 | 57.8 ± 6.5 | 34.5 ± 1.2 | 43.7 ± 2.7 (2.6) | 44.6 ± 1.3 (2.6) | 115.5 ± 10.1 |
| P12 | 73.5 ± 3.8 | 24.0 ± 2.0 | 55.5 ± 3.5 | 32.6 ± 2.1 | 32.6 ± 2.4 |
| P13 | 93.4 ± 6.4 | 153.5 ± 2.9 | 181.4 ± 4.7 | 52.8 ± 2.2 | 91.6 ± 4.1 |
| P14 | 25.8 ± 2.7 | 33.3 ± 1.7 | 17.8 ± 0.5 (2.0) | 42.5 ± 2.8 (0.8) | 35.1 ± 2.8 |
| P15 | 58.5 ± 3.4 | 36.0 ± 3.9 | 42.9 ± 1.0 | 98.0 ± 5.5 | 53.7 ± 3.1 |
| P16 | 46.0 ± 1.0 | 39.1 ± 2.3 | 21.0 ± 1.3 (2.6) | 19.6 ± 2.0 (2.8) | 54.2 ± 3.6 |
| P17 | 44.5 ± 3.0 | 34.2 ± 3.9 | 19.7 ± 0.8 (3.7) | 23.4 ± 1.7 (3.1) | 72.4 ± 6.0 |
| P18 | 48.0 ± 2.1 | 19.3 ± 2.4 | 25.9 ± 0.9 (2.0) | 21.9 ± 0.2 (2.3) | 49.6 ± 1.5 |
| P19 | 47.1 ± 4.2 | 40.5 ± 3.0 | 7.6 ± 0.6 (7.5) | 97.9 ± 5.6 (0.6) | 57.0 ± 1.3 |
| P20 | 109.8 ± 15.4 | 50.0 ± 4.3 | 119.6 ± 2.6 | 57.3 ± 0.2 | 47.7 ± 2.7 |
| P21 | 67.8 ± 2.3 | 42.7 ± 4.0 | 58.6 ± 2.3 | 37.8 ± 3.2 | 50.1 ± 6.5 |
| P22 | 28.7 ± 1.2 | 31.3 ± 2.4 | 12.6 ± 1.6 (3.8) | 18.7 ± 1.4 (2.6) | 47.6 ± 1.6 |
| P23 | 31.2 ± 1.5 | 27.4 ± 2.3 | 23.9 ± 1.0 (1.7) | 21.7 ± 1.9 (1.9) | 40.5 ± 1.5 |
| P24 | 56.4 ± 1.7 | 54.1 ± 1.9 | 18.6 ± 0.9 (3.3) | 140.8 ± 3.9 (0.4) | 60.4 ± 3.2 |
| P25 | 14.3 ± 0.9 | 7.6 ± 0.6 | 3.7 ± 0.5 (8.2) | 12.2 ± 0.6 (2.5) | 30.5 ± 2.0 |
| Celecoxiba | 26.8 ± 2.7 | 11.4 ± 2.4 | 7.4 ± 0.6 (6.7) | 44.1 ± 1.1 (1.1) | 49.8 ± 8.2 |
| Cisplatinb | 1.49 ± 0.44 | 14.2 ± 0.24 | 7.7 ± 0.3 (0.4) | 4.4 ± 0.2 (0.8) | 3.4 ± 0.4 |
SI: a selectivity index was calculated as the IC50 value in the respective normal cells (HaCaT keratinocytes) divided by the IC50 for the specified cancer cell lines. IC50: expresses the compound concentration capable of inhibiting the maximal measured cell proliferation (assessed as cell viability of the cultured cells) by 50%.
aCelecoxib and bcisplatin (a known anticancer agent) served as positive controls. Data are expressed as mean ± SD from the response vs. concentration curves of at least six independent experiments carried out in quadruplicate.