Table 2.
In vitro antimalarial activity of SB939
| Compound |
P. falciparum IC50 (μM) |
Mammalian cell IC50 (μM)a |
Selectivity indexb | ||||
|---|---|---|---|---|---|---|---|
| 3D7 | Dd2 | NHDF cells | HUVEC | PTC | NFF cells | ||
| SAHA | 0.12 ± 0.04 | 0.19 ± 0.01 | 2.0 ± 0.04 | 1.8 ± 0.2 | 3.0 ± 0.5 | 4.90 ± 1.24 | 9–49 |
| SB939 | 0.08 ± 0.03 | 0.15 ± 0.03 | >100 | 0.8 ± 0.1 | 3.2 ± 0.5 | 1.48 ± 0.61 | 4–>1,250 |
| Chloroquine | 0.03 ± 0.09 | 0.15 ± 0.04 | >900 | ND | ND | 39.53 ± 1.32 | 258–>30,000 |
a
SAHA cytotoxicity was previously tested against NHDF cells (20); SB939 cytotoxicity was previously tested against NHDF cells (47); SB939 and SAHA cytotoxicity was tested in this study against HUVEC, PTC, and NFF cells; and chloroquine cytotoxicity was tested in this study against NFF cells and in previous studies against NHDF cells (55). ND, not determined.
b
Mammalian cell IC50/P. falciparum IC50. Larger values indicate greater parasite selectivity.