Activity-guided isolation of antiplasmodial dihydrochalcones and flavanones from Piper hostmannianum var. berbicense.
The bioassay-guided purification of an n-hexane extract from the leaves of Piper hostmannianum var. berbicense led to the isolation of four monoterpene or prenyl-substituted dihydrochalcones (1a, 1b, 2, 3) as well as the known compounds 2',6'-dihydroxy-4'-methoxydihydrochalcone (4), linderatone (5), strobopinin (6), adunctin E (7) and (-)-methyllinderatin (8). Their structures were established on the basis of NMR and X-ray analysis. (-)-Methyllinderatin, linderatone and 2',6'-dihydroxy-4'-methoxydihydrochalcone exhibited the most potent antiplasmodial activity with IC50 values of 5.64, 10.33 and 12.69 microM, respectively against both chloroquine-sensitive and resistant strains of Plasmodium falciparum (F32,FcB1). The activity of (-)-methyllinderatin was confirmed in vivo against Plasmodium vinckei petteri in mice (80% of reduction of parasitemia) at a dose of 20 mg/kg/day.
Portet
Bénédicte
B
UMR 152, IRD - Université Paul Sabatier Toulouse 3, Faculté des Sciences Pharmaceutiques, 31062 Toulouse Cedex 09, France.
Fabre
Nicolas
N
Roumy
Vincent
V
Gornitzka
Heinz
H
Bourdy
Geneviève
G
Chevalley
Séverine
S
Sauvain
Michel
M
Valentin
Alexis
A
Moulis
Claude
C
D000818:Animals; D000962:Antimalarials / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D047188:Chalcones / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D005260:Female; D044950:Flavanones / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D008288:Malaria / Q000188:drug therapy; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D031701:Piper / Q000737:chemistry*; D010961:Plasmodium / Q000187:drug effects
D000962:Antimalarials; D047188:Chalcones; D044950:Flavanones