FIG 2.

(a) Inhibition of proliferation of P. falciparum parasites (chloroquine-sensitive strain 3D7) by α-Me-N-PE-PanAm. Parasites were cultured for 96 h in medium with (○) or without (●) pantetheinase activity; the inhibition was antagonized when the extracellular pantothenate concentration in the medium with pantetheinase was increased from the usual 1 μM to 100 μM (△), consistent with the compound being on target. Values represent the mean ± SEM of three independent experiments, each performed in triplicate. (b) Pantetheinase-mediated hydrolysis of N-PE-PanAm (black bar) and α-Me-N-PE-PanAm (gray bar) in vitro after treatment with recombinant human pantetheinase for 24 h. The amount of phenethylamine released was determined by derivatization with fluorescamine. Values represent the mean from two independent experiments, each performed in triplicate; the error bars represent range/2. **, P < 0.001, Student's t test. (c) HFF proliferation in the presence of α-Me-N-PE-PanAm after 96 h. Values represent the mean ± SEM of three independent experiments, each performed in triplicate.