In vitro studies on the mechanism of action of two compounds with antiplasmodial activity: ellagic acid and 3,4,5-trimethoxyphenyl(6'-O-aalloyl)-beta-D-glucopyranoside.
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.
Dell'Agli
Mario
M
Parapini
Silvia
S
Basilico
Nicoletta
N
Verotta
Luisella
L
Taramelli
Donatella
D
Berry
Colin
C
Bosisio
Enrica
E
D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004610:Ellagic Acid / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D005960:Glucosides / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy; D027822:Myrtaceae; D021261:Parasitic Sensitivity Tests; D008517:Phytotherapy; D024301:Plant Bark; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D010963:Plasmodium falciparum / Q000187:drug effects*
C433900:3,4,5-trimethoxyphenyl-(6'-O-galloyl)-O-glucopyranoside; D000962:Antimalarials; D005960:Glucosides; D010936:Plant Extracts; D004610:Ellagic Acid