Table 2.
Growth inhibition (GI50/μM)a data for (Z)-indole-3-yl (21–24) and (Z)-benzo[b]furan-3-yl (25) cyanocombretastatin analogues
| Panel/cell line | 21 | 22 | 23 | 24 | 25 |
|---|---|---|---|---|---|
|
| |||||
| μM | μM | μM | μM | μM | |
| Leukemia | |||||
| CCRF-CEM | 0.058 | 2.74 | 0.042 | 0.064 | 1.41 |
| HL-60(TB) | 0.048 | 4.57 | 0.031 | 0.059 | 1.03 |
| K-562 | 0.040 | 1.65 | 0.043 | 0.044 | 0.513 |
| MOLT-4 | 0.131 | 3.99 | 0.049 | 0.198 | 3.82 |
| RPMI-8226 | 0.231 | 3.96 | 0.065 | 0.241 | 2.47 |
| SR | 0.022 | 1.45 | 0.033 | 0.027 | 0.681 |
| Lung Cancer | |||||
| A549/ATCC | 0.078 | 5.16 | 0.061 | 0.086 | 0.665 |
| EKVX | 0.596 | 18.5 | 0.478 | 0.485 | na |
| HOP-62 | 0.082 | 8.69 | 0.273 | 0.133 | 6.98 |
| HOP-92 | 1.01 | 5.26 | 0.068 | 0.083 | 3.02 |
| NCI-H226 | 0.194 | 20.9 | 8.18 | 0.170 | 6.20 |
| NCI-H23 | 0.133 | 7.19 | 0.256 | 0.101 | 4.58 |
| NCI-H322M | nd | 24.3 | nd | 0.044 | 19.1 |
| NCI-H460 | 0.041 | 4.51 | 0.039 | 0.037 | 0.839 |
| NCI-H522 | 0.037 | 3.05 | 0.027 | 0.086 | 0.261 |
| Colon Cancer | |||||
| COLO 205 | 0.474 | 5.31 | 0.047 | 0.051 | 0.449 |
| HCC-2998 | 0.107 | 12.6 | 0.207 | 0.119 | 4.13 |
| HCT-116 | 0.048 | 35.5 | 0.042 | 0.045 | 0.517 |
| HCT-15 | 0.051 | 3.70 | 0.053 | 0.068 | 0.492 |
| HT29 | 0.038 | 3.32 | 0.038 | 0.038 | 0.394 |
| KM12 | 0.043 | 4.04 | 0.040 | 0.044 | 0.586 |
| SW-620 | 0.047 | 3.53 | 0.044 | 0.046 | 0.504 |
| CNS Cancer | |||||
| SF-268 | 2.54 | 18.9 | 0.078 | 2.14 | 4.79 |
| SF-295 | 0.042 | 4.92 | 0.045 | 0.042 | 0.446 |
| SF-539 | 0.099 | 8.42 | 0.052 | 0.071 | 0.442 |
| SNB-19 | 0.076 | 24.2 | 0.062 | 0.089 | 3.63 |
| SNB-75 | 0.042 | 6.04 | 0.034 | 0.043 | 0.769 |
| U251 | 0.050 | 4.97 | 0.045 | 0.050 | 0.605 |
| Melanoma | |||||
| LOX IMVI | 0.075 | 5.32 | 0.078 | 0.074 | 0.993 |
| MALME-3M | 12.5 | 9.91 | nd | 5.85 | 0.868 |
| M14 | 0.053 | 3.75 | 0.042 | 0.052 | 0.667 |
| MDA-MB-435 | 0.024 | 3.95 | 0.020 | 0.027 | 0.278 |
| SK-MEL-2 | na | 4.70 | 0.051 | na | 0.304 |
| SK-MEL-28 | 0.090 | 6.25 | 0.081 | 0.092 | 1.61 |
| SK-MEL-5 | 0.042 | 4.27 | 0.048 | 0.036 | 0.336 |
| UACC-257 | 11.3 | 11.9 | nd | 10.7 | nd |
| UACC-62 | 0.048 | 6.98 | 0.049 | 0.059 | 0.519 |
| Ovarian Cancer | |||||
| IGROV1 | 0.417 | 21.0 | 0.347 | 0.379 | 3.06 |
| OVCAR-3 | 0.033 | 5.68 | 0.031 | 0.034 | 0.277 |
| OVCAR-4 | 0.338 | 22.1 | 3.52 | 1.35 | 2.61 |
| OVCAR-5 | 10.6 | >100 | 0.197 | 0.516 | 3.33 |
| OVCAR-8 | 0.121 | 7.38 | 0.103 | 0.148 | 2.90 |
| NCI/ADR-RES | 0.039 | 1.70 | 0.033 | 0.037 | 0.382 |
| SK-OV-3 | 0.051 | 11.9 | 0.117 | 0.056 | 1.71 |
| Renal Cancer | |||||
| 786-0 | 0.090 | 14.1 | 0.077 | 0.085 | 6.11 |
| A498 | 0.035 | 3.36 | 0.035 | 0.025 | 0.458 |
| ACHN | 1.76 | 23.7 | nd | 1.66 | 1.94 |
| CAKI-1 | 0.058 | 4.34 | 0.035 | 0.072 | 0.650 |
| RXF 393 | 0.036 | 4.48 | 0.083 | 0.033 | 0.496 |
| SN12C | 0.699 | 8.10 | 0.077 | 0.715 | 2.17 |
| TK-10 | 11.1 | 13.2 | 10.3 | 20.1 | 2.10 |
| UO-31 | 1.41 | 14.3 | 0.663 | 1.26 | 2.89 |
| Prostate Cancer | |||||
| PC-3 | 0.054 | 7.85 | 0.075 | 0.054 | 1.84 |
| DU-145 | 0.132 | 22.6 | 0.130 | 0.153 | 1.88 |
| Breast Cancer | |||||
| MCF7 | 0.034 | 3.10 | 0.041 | 0.036 | 0.376 |
| MDA-MB-231/ATCC | 0.245 | 7.18 | 0.644 | 0.299 | 1.71 |
| HS 578T | 0.131 | 12.9 | 0.611 | 0.124 | 2.03 |
| BT-549 | 1.94 | 5.38 | 0.049 | 0.348 | 0.927 |
| T-47D | 0.058 | 6.83 | nd | 0.065 | 0.811 |
| MDA-MB-468 | 0.041 | na | 0.051 | 0.035 | 0.237 |
na: Not analyzed, nd: not determined,
GI50: 50% growth inhibition, concentration of drug resulting in a 50% reduction in net cell growth as compared to cell numbers on day 0.