Table 2. Effects of the identified MMV Pathogen Box compounds on P. falciparum proliferation.
Determination of the inhibitory properties of the identified compounds on the proliferation of P. falciparum parasite strains, including WT 3D7, yeast dihydroorotate dehydrogenase (yDHODH)-expressing 3D7, and ATVR 3D7 and the equivalent ATV-sensitive parental WT 3D7 strain. As the yDHODH and ATVR strains were generated in different laboratories, proliferation of the WT 3D7 background strain of each was determined for comparisons. Data are reported as average EC50 (nM) ± SEM from three or more independent experiments. The fold change (FC) was calculated by dividing the EC50 against ATVR parasites by the EC50 against WT parasites, with FC values >1 indicating increased resistance to the tested compounds in the ATVR strain. Paired t-tests were performed to compare the EC50 of the compounds in WT vs ATVR parasites, and p-values are depicted as ns = not significant (p > 0.05), * p < 0.05, ** p < 0.01. ND = not determined.
| P. falciparum | |||||
|---|---|---|---|---|---|
| WT | yDHODH | WT | ATVR | ||
| Compound | EC50 (nM) | EC50 (nM) | EC50 (nM) | EC50 (nM) | FC |
| Atovaquone | 0.13 ± 0.02 | > 10 | 0.31 ± 0.04 | 7.6 ± 0.9 | 24 ** |
| Chloroquine | 6.6 ± 1.3 | 7.70 ± 0.07 | 19 ± 2 | 19 ± 3 | 1 ns |
| Buparvaquone | 1.2 ± 0.3 | > 12.5 | 10.9 ± 1.2 | 1,160 ± 215 | 106 * |
| Auranofin | 2,040 ± 410 | 1,810 ± 490 | 2,831 ± 503 | 2,783 ± 362 | 1 ns |
| Trifloxystrobin | 44 ± 16 | > 250 | 33 ± 7 | 131 ± 12 | 4 * |
| Azoxystrobin | 23 ± 9 | > 125 | 12 ± 1 | 31 ± 7 | 2.6 ns |
| MMV024397 | 308 ± 18 | 3,740 ± 1,280 | 400 ± 48 | 602 ± 93 | 1.5 * |
| MMV688853 | > 6,250 | > 6,250 | >40,000 | >40,000 | ND |