Table 1. Potency of TCNs against Plasmodium spp.
| compound | P. falciparum ABS (W2) EC50, nM (pEC50) | HepG2 Tox CC50, nM (pCC50) | ABS-HepG2 SI | P. vivax schizontb EC50, nM (pEC50) | P. vivax hypnozoite EC50, nM (pEC50) | PHH Tox CC50, nM (pCC50) | schizontb-PHH SI | hypno-zoite -PHH SI |
|---|---|---|---|---|---|---|---|---|
| anguidine | 6.16 (8.21 ± 0.06) | 27.5 (7.56 ± 0.08) | 4.43 | 13.5 (7.87 ± 0.55) | 36.3 (7.44 ± 0.75) | 380 (6.42 ± 0.31) | 28.7 | 10.7 |
| verrucarin A | 0.45 (9.35 ± 0.04) | 3.55 (8.45 ± 0.18) | 7.95 | 4.07 (8.39 ± 0.82) | 30.9 (7.51 ± 0.11) | 316 (6.50 ± 0.05) | 77.7 | 10.1 |
| verrucarol | >4370 (<5.36 ± 0.20) | >10 000 (<5.00 ± 0.00) | N/A | >10 000 (<5.00 ± 0.00) | >3311 (<5.48 ± 0.68) | >10 000 (<5.00 ± 0.00) | N/A | N/A |
| dihydroart-emisinina | 1.44 (8.84 ± 0.09) | |||||||
| puromycina | 398 (6.40 ± 0.10) | 2290 (5.64 ± 0.47) | 776 (6.11 ± 0.07) | 1740 (5.76 ± 0.00) | <1.00 | 2.25 | ||
| nigericina | 5.13 (8.29 ± 0.25) | 12.3 (7.91 ± 0.25) | >200 (6.70 ± 0.00) | >38.9 | >16.3 |
a
Positive control.
b
P. vivax liver schizonts; ABS (W2), asexual blood stage strain W2; HepG2 Tox, HepG2 cytotoxicity; SI, selectivity index; PHH Tox, primary human hepatocyte cytotoxicity. Shown are the geometric means of all EC50 values from all independent experiments, as well as the pEC50 or pCC50 values (i.e., the −log of EC50 or CC50 in [M]) including the standard deviation from all independent experiments in parentheses.