Figure 2: Evolution of resistance to quinoxaline-containing compounds.

A) Selection scheme showing attempts to generate resistance using the Dd2-Pol𝛿 mutator line. Indicated are the compound, parasite inoculum, selection period during which parasites were exposed to 5xIC₅₀, recrudescence status of cultures, and shift in IC₅₀ of the bulk culture. B) Clones from two independent flasks (1.1 and 2.1) from the compound 22 selection were evaluated against compounds 22 and 31. The parental line, Dd2-Pol𝛿 (Pol𝛿) was used as the control. C) Clones (1.1 and 2.1) from the compound 22 selection were evaluated against other quinoxaline-containing compounds, MMV665794, MMV007224 and BQR695. Each dot represents a biological replicate (n=4–6) with mean±SD shown as bar chart, and statistical significance determined by Mann-Whitney U test (*p<0.05, **p<0.01).