FIG 5.

(A) Relative abundance (peak height) of dihydroorotate and N-carbamoyl-l-aspartate in P. falciparum-infected erythrocytes after treatment with all compounds (mean ± standard deviation; n = 4). Compounds that induced significant (α = 0.05) accumulation are labeled (see Table 1 for MMV identifiers). (B) Simplified schematic of the de novo pyrimidine biosynthesis pathway indicating the targets of atovaquone and DSM265. (C) ¹³C enrichment from [¹³C₁]bicarbonate in pyrimidine intermediates following 2 h of treatment with atovaquone, G5, G7, and G8, expressed as the percent difference from drug-free controls. Metabolite abundance in these samples, relative to drug-free controls, is shown in the lower panels. (D) Concentration-response profiles for representative pyrimidine biosynthesis inhibitors and atovaquone in 48-h growth inhibition assays using wild-type 3D7 (blue) and yDHODH-expressing (red) P. falciparum iRBCs.