TABLE X.
Enzyme-Based Histone Deacetylase (HDAC) and DNA Methyltransferase (DNMT) Inhibition Data, and Cell-Based p21 Promoter Activity Data, for the Psammaplins (112).
| Alkaloids | HDAC enzyme inhibition IC50 (nM)a | cell-based fold induction activity AC50 (μM)b | max fold induction (22 MFI is produced at 0.5 μM) | DNMT enzyme inhibition IC50 (nM) |
|---|---|---|---|---|
| Psammaplin A (152) | 4.2 ± 2.4 | 7.5 | 15 | 18.6 |
| Psammaplin B (156) | 48 ± 12 | 15.0 | 7 | nt |
| Psammaplin C (157) | nt | nt | nt | nt |
| Psammaplin D (158) | 44 ± 10 | > 15.0 | 5 | > 30.0 |
| Psammaplin E (159) | 327 ± 39 | > 15.0 | 2 | > 30.0 |
| Psammaplin F (160) | 2.1 ± .4 | 0.7 | 18 | > 30.0 |
| Psammaplin G (161) | 18 ± 8 | 7.5 | 7 | 12.8 |
| Psammaplin H (162) | 79 ± 22 | 3.8 | 7 | > 30.0 |
| Psammaplin I (163) | 299 ± 70 | 2.6 | 9 | > 30.0 |
| Psammaplin J (164) | 20 ± 17 | 3.6 | 8 | nt |
| Bisaprasin (154) | 9 ± 5 | 0.7 | 9 | 3.4 |
| Trichostatin A | 14 ± 1 | 0.2 | 7.2 | nt |
| Trapoxin A | 9 ± 3 | 0.005 | 28.5 | nt |
a
Compounds were titrated in a 1:5 dilution series (10 μM, 2 μM, 400 nM, 80 nM, and 16 nM); averages from duplicate trials are shown, except for known HDAC inhibitors, trichostatin A and trapoxin A.
b
Concentration of compound required to produce 50% p21 promoter activity by psammaplin A (152).