Table 4. In Vitro Cytotoxicity (CHO), hERG Channel Activity, and Microsomal Metabolic Stability Data of Selected Analogues.
| cytotoxicity (CHO)a |
hERGb |
||||
|---|---|---|---|---|---|
| compound | IC50 (μM) | SIc | IC50 (μM) | SIc | clogPd |
| AST | 29.6 | 344 | 0.0042 | 0.049 | 5.70 |
| 3 | 0.41 | 1.24 | 4.65 | ||
| 12 | 0.09 | 0.16 | 3.80 | ||
| 14 | 0.05 | 0.32 | 4.70 | ||
| 16 | 0.11 | 0.23 | 4.07 | ||
| 18 | 4.16 | >0.7 | 4.45 | ||
| 21 | >50 | >2000 | 0.97 | 38.8 | 4.83 |
| 24 | 47.4 | 667 | 0.05 | 0.70 | 4.85 |
| 30 | 5.36 | 153 | 5.71 | ||
| 32 | 12.4 | 289 | 5.22 | ||
| 34 | 42.3 | 631 | 5.69 | ||
| 46 | 29.5 | 148 | 8.61 | 43.3 | 3.49 |
| verapamil | 0.2–0.8 | ||||
| emetine | 0.95 | ||||
a
CHO: Chinese hamster ovary epithelial cell line. Mean value from n = 3 independent experiments. Emetine (IC50 = 0.033 μM) was used as the reference drug.
b
hERG: Human ether-a-go-go-related gene. Mean value from n = 3 independent experiments. Verapamil (IC50 = 0.56 ± 0.096 μM) as a reference.
c
SI: Selectivity index = [CHO IC50/PfNF54 IC50] or [hERG IC50/PfNF54 IC50].
d
Calculated using StarDrop software v6.5-1-1.