Covalent Plasmodium falciparum-selective proteasome inhibitors exhibit a low propensity for generating resistance in vitro and synergize with multiple antimalarial agents
Fig 2
WLL- and WLW-pressured mutant parasite lines display modest gains of resistance.
(A and B) Mean ± SEM IC50 values are shown for the Cam3.II or V1/S lines expressing (blue) WT or (red) C580Y K13, exposed to (A) WLL or (B) WLW for 72 hr. Assays were performed on five to seven independent occasions in duplicate. Shown above each bar is the compound used for resistance selections (thin hatching, WLL-selected; thick hatching, WLW-selected). Mutant lines (see Table 2 and S7 Table) are illustrated beside their parental drug-sensitive line. Statistical significance was examined using Mann-Whitney U tests. **P value <0.01; ns, not significant. IC50 and IC90 values and associated statistics are reported in S8 Table and S9 Table, respectively.