Table 3.
Inhibition of growth of CFPAC-1 human pancreatic cancer, DMS-53 human SCLC, PC-3 human prostate cancer, and MKN-45 human gastric cancer cell lines by DOX, 2-pyrrolino-DOX (AN-201), and the corresponding cytotoxic BN analogs
| Compound | IC50,* 10−10 M
|
|||
|---|---|---|---|---|
| CFPAC-1 at 120 hr | DMS-53 at 140 hr | PC-3 at 72 hr | MKN-45 at 115 hr | |
| Analogs with DOX | ||||
| AN-253 | 530 (180)† | 640 (≪300) | 2100 (760) | 2700 (500) |
| AN-246 | 650 | 490 | 2700 | 3600† |
| AN-161 | 760 | 780 | 3500† | 5100† |
| AN-160 | 580 | 530 | 3200† | 2300 |
| AN-251 | 630 | 370 | 2600 | 2000 |
| DOX | 570 | 580 | 1500 | 1800 |
| Analogs with AN-201 | ||||
| AN-254 | 1.8 | 0.33 | 6.1 | 2.1 |
| AN-247 | 2.0 | 0.37 | 6.8 | 2.9 |
| AN-257 | 1.7 | 0.35 | 6.7 | 2.1 |
| AN-215 | 2.7 | 0.41 | 6.8 | 2.4 |
| AN-252 | 3.5 | 0.46 | 13.0† | 3.7 |
| AN-201 | 1.6 | 0.22† | 3.6 | 1.5 |
Cell growth inhibition data, determined at three different concentrations as shown in Table 2, were used to calculate the drug concentration that inhibited cell growth by 50%, as compared with untreated control cultures. All data were derived from an average of three determinations each in eight replicates. CFPAC-1 and DMS-53 cells were grown under conditions described in Table 2. PC-3 cells were incubated in RPMI 1640:F12 (1:1) medium containing 1 mM pyruvate/1 μM FeSO4/0.5% bovine serum albumin. MKN-45 cells were incubated in Dulbecco’s modified Eagle medium containing 10% FBS.
Values calculated by extrapolation. IC50 values in brackets are derived from results with a sample of AN-253 containing decomposition products.