Fig 1. P. falciparum mutant PfCRT-mediated resistance to piperaquine (PPQ), unlike the related 4-aminoquinoline chloroquine (CQ), cannot be explained solely by reduced intracellular drug accumulation.

Cellular accumulation ratios (CAR) represent the ratio of intracellular to extracellular (A) [³H]-PPQ and (C) [³H]-CQ and were measured after 1 hr incubation at 37°C. Results were plotted against (B) PPQ and (D) CQ in vitro antiplasmodial activities as indexed by their 90% growth inhibitory concentrations (IC₉₀). Assays employed synchronized trophozoites, when the DV is fully formed and Hb degradation is maximal. CAR, IC₅₀ and IC₉₀ results for each line are presented as the mean ± SEM value (4 to 5 independent experiments with technical duplicates; see S1 Table and raw data in S1 Data). Statistical significance was determined using Mann–Whitney U tests comparing the pfcrt-edited lines with their isogenic Dd2^Dd2crt parent. *p<0.05; **p<0.01; ns; not significant.