Table 2.
Susceptibility of P. knowlesi and P. falciparum to three DHODH inhibitors assessed using the SYBR Green I assay
DHODH inhibitor | EC50 (nM), single life cycle |
EC50 (nM), two life cycles |
||||
---|---|---|---|---|---|---|
P. knowlesi, 27 h | P. falciparum, 48 h | fold difference | P. knowlesi, 54 h | P. falciparum, 96 h | fold difference | |
DSM1 | 509 ± 11 | 149 ± 5 | 3.4 | 417 ± 2 | 91 ± 10 | 4.6 |
DSM265 | 303 ± 15 | 37 ± 3 | 8.2 | 186 ± 11 | 21 ± 1 | 8.9 |
DSM421 | 194 ± 23 | 72 ± 5 | 2.7 | 123 ± 10 | 42 ± 4 | 2.9 |
All inhibitors were tested in duplicate on three separate occasions from a starting parasitaemia and haematocrit of 1%. The EC50 values are reported as the mean ± SEM. The fold difference is calculated by dividing the P. knowlesi EC50 value by the P. falciparum EC50 value. For each DSM compound, the mean P. falciparum EC50 value was significantly lower than the mean P. knowlesi EC50 value when compared over either a single parasite life cycle or over two life cycles (P ≤ 0.0018).