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To investigate the mechanism of action of two antiplasmodial compounds, ellagic acid and 3,4,5-trimethoxyphenyl (6'-O-galloyl)-beta-D-glucopyranoside (TMPGG), we studied in vitro two metabolic reactions of intraerythrocytic parasites: the activity of recombinant plasmepsin II, one of the haemoglobin proteases, and the detoxification of haematin into beta-haematin. Both compounds inhibited plasmepsin II activity, but at concentrations ten-fold higher than those needed for inhibiting parasite growth. Moreover, ellagic acid inhibited the formation of beta-haematin, with an IC50 only 3-fold higher than that of chloroquine. These data suggest that the antiplasmodial activity of ellagic acid could be related to the inhibition of beta-haematin formation, whereas plasmepsin II does not represent the main target of the two compounds.

planta medica

<i>In Vitro</i>Studies on the Mechanism of Action of Two Compounds with Antiplasmodial Activity: Ellagic Acid and 3,4,5-Trimethoxyphenyl(6′-<i>O</i>-Galloyl)-β-<scp>D</scp>-glucopyranoside

In VitroStudies on the Mechanism of Action of Two Compounds with Antiplasmodial Activity: Ellagic Acid and 3,4,5-Trimethoxyphenyl(6′-O-Galloyl)-β-D-glucopyranoside