Table 1.
Growth inhibition (GI50/μM)a data for (Z)-indol-2-yl (8, 11), (Z)-benzo[b]furan-2-yl (12, 13), and (Z)-benzo[d]thiazol-2-yl (15, 17) cyano combretastatin analogues
| Panel/cell line | 8 | 9 | 11 | 12 | 13 | 15 | 17 |
|---|---|---|---|---|---|---|---|
|
| |||||||
| μM | μM | μM | μM | μM | μM | μM | |
| Leukemia | |||||||
| CCRF-CEM | 0.017 | 0.062 | 0.136 | 0.024 | 0.777 | 0.055 | na |
| HL-60(TB) | <0.01 | 0.034 | 0.031 | <0.01 | 0.481 | 0.066 | 0.345 |
| K-562 | <0.01 | 0.039 | 0.039 | <0.01 | 0.467 | 0.051 | 0.333 |
| MOLT-4 | 0.023 | 0.084 | 0.274 | 0.047 | 0.548 | 9.20 | 3.38 |
| RPMI-8226 | <0.01 | 0.151 | 0.199 | 0.019 | 1.32 | 0.237 | 2.29 |
| SR | <0.01 | 0.042 | na | <0.01 | 0.470 | 0.107 | 0.402 |
| Lung Cancer | |||||||
| A549/ATCC | <0.01 | 0.114 | 0.076 | <0.01 | 0.520 | 0.379 | na |
| EKVX | 1.16 | 0.307 | na | 0.059 | na | na | na |
| HOP-62 | <0.01 | na | 0.092 | <0.01 | 2.29 | 1.93 | 3.35 |
| HOP-92 | <0.01 | 0.058 | 0.077 | <0.01 | 1.13 | nd | 0.534 |
| NCI-H226 | <0.01 | 0.399 | 14.5 | <0.01 | 34.5 | 0.844 | 4.11 |
| NCI-H23 | <0.01 | 0.236 | 0.246 | <0.01 | 3.11 | 3.25 | 2.84 |
| NCI-H322M | nd | 0.735 | 0.465 | <0.01 | 6.18 | 2.29 | >10.0 |
| NCI-H460 | <0.01 | 0.053 | 0.093 | <0.01 | 0.472 | 0.336 | 2.86 |
| NCI-H522 | <0.01 | 0.049 | 0.033 | <0.01 | 0.438 | 0.022 | na |
| Colon Cancer | |||||||
| COLO 205 | 0.016 | 0.232 | 0.097 | <0.01 | 0.404 | 0.036 | 0.574 |
| HCC-2998 | 0.018 | 0.366 | 0.265 | 0.01 | 2.33 | 0.297 | 8.39 |
| HCT-116 | <0.01 | 0.044 | 0.047 | <0.01 | 0.418 | 0.052 | 0.404 |
| HCT-15 | <0.01 | 0.048 | 0.089 | <0.01 | 0.469 | 0.045 | 0.414 |
| HT29 | <0.01 | 0.048 | 0.048 | <0.01 | 0.373 | 0.037 | 0.438 |
| KM12 | <0.01 | 0.076 | 0.047 | <0.01 | 0.356 | 0.278 | 2.01 |
| SW-620 | <0.01 | 0.042 | 0.048 | <0.01 | 0.388 | 0.038 | 0.343 |
| CNS Cancer | |||||||
| SF-268 | 0.015 | 1.48 | 0.086 | 0.247 | 2.05 | 1.03 | 3.09 |
| SF-295 | <0.01 | 0.036 | 0.037 | <0.01 | 0.708 | 0.508 | 2.46 |
| SF-539 | <0.01 | 0.047 | 0.039 | <0.01 | 1.56 | 0.097 | 1.68 |
| SNB-19 | <0.01 | 0.189 | 0.085 | <0.01 | 5.55 | 2.49 | >10.0 |
| SNB-75 | <0.01 | 0.036 | 0.039 | <0.01 | 1.78 | 0.145 | 2.13 |
| U251 | <0.01 | 0.075 | 0.044 | <0.01 | 0.760 | 1.65 | 1.91 |
| Melanoma | |||||||
| LOX IMVI | <0.01 | 0.064 | 0.090 | <0.01 | 0.930 | 0.073 | 1.84 |
| MALME-3M | 8.28 | nd | nd | 59.9 | 0.629 | 0.515 | 0.699 |
| M14 | <0.01 | 0.039 | 0.056 | <0.01 | 0.437 | 0.193 | 1.21 |
| MDA-MB-435 | <0.01 | 0.021 | 0.024 | <0.01 | 0.229 | 0.021 | 0.199 |
| SK-MEL-2 | <0.01 | 0.312 | 0.528 | <0.01 | 0.487 | 0.287 | 0.958 |
| SK-MEL-28 | na | 1.94 | 0.161 | <0.01 | 3.51 | 1.81 | 1.98 |
| SK-MEL-5 | <0.01 | 0.142 | 0.060 | <0.01 | 0.564 | 0.100 | 1.37 |
| UACC-257 | 1.06 | 27.0 | 0.062 | 63.2 | 18.0 | >100 | na |
| UACC-62 | <0.01 | 0.038 | 0.058 | <0.01 | 0.557 | 0.052 | 0.755 |
| Ovarian Cancer | |||||||
| IGROV1 | <0.01 | 0.482 | 0.183 | 0.022 | 1.27 | 1.27 | 0.706 |
| OVCAR-3 | <0.01 | 0.034 | 0.042 | <0.01 | 0.279 | 0.031 | 0.285 |
| OVCAR-4 | 15.2 | 0.735 | 0.672 | 0.039 | 7.19 | 3.86 | >10.0 |
| OVCAR-5 | 0.08 | 0.471 | 0.259 | 0.042 | 5.23 | 0.347 | 4.85 |
| OVCAR-8 | <0.01 | 0.326 | 0.124 | <0.01 | 3.98 | 0.438 | 3.13 |
| NCI/ADR-RES | <0.01 | 0.040 | 0.073 | <0.01 | 0.317 | 0.059 | 1.47 |
| SK-OV-3 | <0.01 | 0.394 | 0.087 | <0.01 | 2.49 | 0.626 | 1.79 |
| Renal Cancer | |||||||
| 786-0 | <0.01 | 0.602 | 0.137 | <0.01 | 5.84 | 1.06 | 2.44 |
| A498 | <0.01 | 0.040 | 0.029 | <0.01 | 0.540 | 0.198 | 0.417 |
| ACHN | <0.01 | 0.082 | 0.079 | 0.217 | 12.4 | 0.089 | 0.518 |
| CAKI-1 | <0.01 | 0.103 | 0.035 | <0.01 | 0.492 | 0.047 | 0.482 |
| RXF 393 | <0.01 | 0.151 | 0.055 | <0.01 | 1.30 | 0.148 | 0.551 |
| SN12C | <0.01 | 0.779 | 0.269 | <0.01 | 0.956 | 0.515 | 4.68 |
| TK-10 | <0.01 | 5.56 | 20.1 | 73.6 | 2.28 | 0.063 | 2.78 |
| UO-31 | <0.01 | 0.071 | 0.201 | 2.29 | 3.79 | 0.083 | 0.679 |
| Prostate Cancer | |||||||
| PC-3 | <0.01 | 0.062 | 0.105 | <0.01 | 2.41 | 0.341 | 2.74 |
| DU-145 | <0.01 | 0.206 | 0.207 | <0.01 | 1.30 | 0.333 | 1.07 |
| Breast Cancer | |||||||
| MCF7 | 0.016 | 0.289 | 0.039 | 0.023 | 0.446 | 0.034 | 0.399 |
| MDA-MB-231/ATCC | 0.014 | 0.291 | 0.294 | 0.028 | 1.21 | 0.992 | 6.74 |
| HS 578T | <0.01 | 0.133 | 0.092 | <0.01 | 1.88 | 1.29 | 2.01 |
| BT-549 | <0.01 | 0.0978 | 0.109 | 0.029 | 0.950 | 12.2 | 3.45 |
| T-47D | 2.50 | 0.573 | 95.2 | 4.34 | 0.996 | nd | 1.18 |
| MDA-MB-468 | 0.022 | 0.350 | 0.041 | 0.022 | 0.421 | 0.084 | 2.04 |
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.