Table 4.
Antiproliferative activity of compounds 1–16 in colon carcinoma cells HT-29P (parental), HT-29RNOV (multidrug resistance [MDR] phenotype), and HT-29RBD (multidrug resistance [MDR] phenotype).
| Compound | HT-29P | HT-29RNOV | HT-29RDB | ||
|---|---|---|---|---|---|
| IC50 ± SD (μM) | IC50 ± SD (μM) | RRa | IC50 ± SD (μM) | RRa | |
| Epoxyboetirane E (2) | > 50b | 32.27 ± 4.69 | < 0.65 | 47.21 ± 5.17 | < 0.94 |
| Epoxyboetirane N (6) | > 100 | 48.92 ± 4.92 | < 0.49 | 31.16 ± 0.53 | < 0.31 |
| Epoxyboetirane P (8) | 8.24 ± 0.47 | 5.00 ± 0.16 | 0.61 | 5.25 ± 0.07 | 0.64 |
| Epoxyboetirane R (10) | > 50b | 30.20 ± 4.05 | < 0.60 | > 50b | — |
| Methoxyboetirane B (15) | 20.40 ± 1.83 | 9.40 ± 0.30 | 0.46 | 9.61 ± 0.10 | 0.47 |
| Methoxyboetirane C (16) | 17.20 ± 2.62 | 9.39 ± 0.37 | 0.55 | 13.12 ± 1.15 | 0.76 |
| Cisplatin | 3.8 ± 0.1 | 3.8 ± 0.1 | 1 | 2.7 ± 0.1 | 0.7 |
| Etoposide | 2.3 ± 0.3 | 35.0 ± 2.6 | 15.2 | 26.0 ± 1.7 | 11.3 |
| 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, the IC50 was found to be above 100 µM, except for epoxyboetiranes M (5) and Q (9) which was above 25 µM – the maximum tested concentration 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).