“…The drugs HF, FF, 6F-FF, and Th-FF killed malaria parasites in the very first cycle of erythrocytic development, suggesting that the likely target for these inhibitors was cytoplasmic PfPRS and not apicoplastic PfPRS (Hoen et al, 2013). For each of the four tested inhibitors ( Figure 1A), dose-dependent inhibition followed sigmoidal curves with 50% effective concentration (EC 50 ) in the subnanomolar ranges of 1-190 nM ( Figure 1B), consistent with earlier reports (Derbyshire et al, 2012;Geary et al, 1983;Kikuchi et al, 2006Kikuchi et al, , 2014. The EC 50 values of HF were increased to 5 and 20 nM, respectively, in the presence of 53 and 203 L-Pro (RPMI media supplemented with higher L-Pro concentration) in the culture media, in line with a competitive inhibition mode of binding in context of the PRS natural substrate L-proline ( Figure 1B).…”