Table 2.
Comparison of the susceptibility of the ex vivo Plasmodium species. Parasites were exposed to serial drug dilutions for a complete life cycle, and [3H]hypoxanthine was added at the beginning of the experiment (see methods section for more details).
| Compound screened | Median EC50 values (nM)a (range) |
Fold Difference (p-value) |
|||||||
|---|---|---|---|---|---|---|---|---|---|
| P. falciparum | P. malariae | P. ovale spp. | P. knowlesi | P. vivax | Pm/Pf | Po/Pf | Pk/Pfb | Pv/Pfb | |
| Chloroquine | 22.61 (3.85–85.0) | 16.38 (9.77–34.4) | 5.69 (4.16–24.3) | 6.18 | 18.46 | 0.72 (0.4247) | 0.25 (0.1130) | 0.27 | 0.82 |
| Dihydroartemisinin | 1.30 (0.94–2.57) | 5.45 (2.27–20.0) | 1.23 (0.77–5.92) | 1.64 | 0.42 | 4.19 (0.0420) | 0.95 (0.5639) | 1.26 | 0.32 |
| Pyronaridine | 0.57 (0.11–1.49) | 2.57 (0.88–4.41) | 1.63 (0.39–7.47) | 1.86 | ND | 4.51 (0.0332) | 2.86 (0.1223) | 3.26 | ND |
| Artefenomel | 0.76 (0.26–1.63) | 1.72 (0.55–2.89) | 0.78 (0.76–0.80) | 3.43 | ND | 2.26 (0.4715) | 1.03 (0.8504) | 4.51 | ND |
| Cipargamin | 1.21 (1.02–1.79) | 6.85 (4.92–8.68) | 8.06 (4.90–17.85) | 9.46 | ND | 5.66 (<0.0001) | 6.66 (0.0038) | 7.82 | ND |
| Ganaplacide | 15.76 (7.65–18.69) | 3.40 (1.18–5.76) | 4.72 (1.30–9.60) | 4.57 | ND | 0.22 (0.0066) | 0.30 (0.0236) | 0.29 | ND |
| DSM265 | 2.51 (0.23–12.18) | 450 (268–511) | 463 (207–769) | 76.4 | 28.2 | 179.3 (0.0064) | 184.5 (0.0105) | 30.44 | 11.24 |
| AN13762 | 226 (45.2–354) | 4166 (2022–8317) | 1708 (776–1789) | 3644 | 2664 | 18.43 (0.0126) | 7.56 (0.0023) | 16.12 | 11.79 |
ND = Not done. No P. vivax EC50 data are available for these compounds.
a
Each EC50 value is determined from the average of a duplicate experiment performed on a single ex vivo sample.
b
No p-value could be calculated as only a single EC50 value was obtained.