Table 3.
Antiproliferative activity of 1–16 in in pancreatic carcinoma cells: EPP85-181P (parental), EPP85-181RNOV (multidrug resistance [MDR] phenotype), and EPP85-181RBD (multidrug resistance [MDR] phenotype).
| Compound | EPP85-181P | EPP85-181RNOV | EPP85-181RDB | ||
|---|---|---|---|---|---|
| IC50 ± SD (μM) | IC50 ± SD (μM) | RRa | IC50 ± SD (μM) | RRa | |
| Epoxyboetirane E (2) | 9.52 ± 0,40 | 41.24 ± 3.54 | 4.33 | 13.18 ± 1.65 | 1.38 |
| Epoxyboetirane M (5) | 17.49 ± 0.08 | > 25 b | > 1.43 | 21.07 ± 2.06 | 1.20 |
| Epoxyboetirane N (6) | 20.63 ± 0.90 | 57.33 ± 4.90 | 2.78 | 14.17 ± 2.34 | 0.69 |
| Epoxyboetirane P (8) | 4.88 ± 0.11 | 5.42 ± 0.49 | 1.11 | 2.57 ± 0.30 | 0.53 |
| Methoxyboetirane B (15) | 12.08 ± 1.84 | 10.01 ± 0.42 | 0.83 | 10.18 ± 0.81 | 0.84 |
| Methoxyboetirane C (16) | 16.51 ± 1.97 | 8.72 ± 0.43 | 0.53 | 20.95 ± 1.79 | 1.27 |
| Etoposide | 0.58 ± 0.0 | 4.5 ± 0.7 | 7.8 | 62.0 ± 4.2 | 106.9 |
| Cisplatin | 0.08 ± 0.0 | 2.6 ± 0.2 | 34 | 0.09 ± 0.0 | 1.2 |
| DMSO (2%) | > 100 | > 100 | — | > 100 | — |
aRelative resistance ratio, RR = IC50(resistant)/IC50(parental)) babove this concentration the compound crystallized in the culture medium. For all the other compounds (1 3, 4, 7 and 11-14), the IC50 values were found to be above 100 µM, except for epoxyboetiranes Q (9) and R (10) which was above 25 µM and 50 µM, respectively, the maximum tested concentrations for each due to lower water solubility. Each IC50 value indicates the mean ± SD of n = 3 to 4 independent experiments (each concentration was performed in triplicate per experiment).