Fig. 7.

In vitro activity of compounds against P. falciparum 3D7 and 3D7- yeast dihydroorotate dehydrogenase parasites in 48 h and 96 h assays. a Compounds were tested in 48 h and 96 h assays against P. falciparum 3D7 and 3D7-yeast dihydroorotate dehydrogenase parasites (3D7-yDHODH), starting with synchronous ring-stage parasites. Mean IC₅₀ ( ± SD) values are shown for 48 h (3D7 solid black bars; 3D7-yDHODH solid grey bars) versus 96 h (3D7 black striped bars; 3D7-yDHODH grey striped bars) assays for each line. Red star—IC₅₀ not achieved (i.e., IC₅₀ greater than value shown). b Fold change in IC₅₀ of compounds against P. falciparum 3D7 and 3D7-yDHODH in 48 h (white bars) and 96 h (chequered bars) assays. Mean IC₅₀ ( ± SD) values were used to compare activity against 3D7-yDHODH versus 3D7 for 48 h and 96 h assays. Solid and dashed horizontal lines show 1× and 10× fold change, respectively. In each case, 2–4 independent experiments were carried out, each in triplicate wells, before data were averaged and fold change calculated. Red star – IC₅₀ not achieved: fold change calculated based on highest concentration tested (i.e., IC₅₀ higher than this value). Selected eukaryote complex I and IV/V mitochondrial electron transport chain inhibitors (sodium azide^52,53, oligomycin A⁵³ and metformin⁵⁴) were examined for comparison purposes