Lupeol long-chain fatty acid esters with antimalarial activity from Holarrhena floribunda.
An ethnopharmacological investigation was conducted among the Baka pygmies of Dja biosphere reserve (Cameroon) to collect information on the antimalarial plants used in their daily life. Holarrhena floribunda is one of those plants. Extracts of the stem barks of H. floribunda showed remarkable inhibitory activity against drug-resistant strains of Plasmodium falciparum at doses of 1.02-18.53 microg/mL when tested in vitro against two parasite clones designated as Indochina (W-2) and Sierra Leone (D-6). The aqueous extract was the most active against Indochina (W-2), with IC50 values of 1.02 microg/mL, while the ethanolic extract appeared to be the most active against Sierra Leone (D-6), with an IC50 of 4.33 microg/mL. The bioassay-guided fractionation of the neutral fraction of the crude extract led to the isolation of lupeol (1) and its three new long-chain fatty acid ester derivatives, namely, 3-O-(3'-hydroxyeicosanoyl)lupeol (2), 3-O-[(2'-(tetracosyloxy)acetyl]lupeol (3), and 3-O-[(1' '-hydroxyoctadecyloxy)-2'-hydroxypropanoyl]lupeol (4). These new compounds displayed some in vitro inhibition activity against the chloroquine-resistant strain FCR-3 isolated from Gambia and the chloroquine-sensitive standard strain 3D7. The hydroxy group of the fatty acid side chain appears to decrease the observed activity.
Fotie
Jean
J
Laboratory of Biological Chemistry, Department of Chemistry, McGill University, Otto Maass Chemistry Building # 230, Sherbrooke Street West, Montreal, Quebec H3A 2K6, Canada. jeanfotie@yahoo.co.uk
Bohle
D Scott
DS
Leimanis
Mara L
ML
Georges
Elias
E
Rukunga
Geoffrey
G
Nkengfack
Augustin E
AE
D000818:Animals; D000962:Antimalarials / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D002163:Cameroon; D004912:Erythrocytes / Q000187:drug effects; D005227:Fatty Acids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D035462:Holarrhena / Q000737:chemistry*; D015394:Molecular Structure; D053978:Pentacyclic Triterpenes; D024301:Plant Bark / Q000737:chemistry; D010946:Plants, Medicinal / Q000737:chemistry*; D010963:Plasmodium falciparum / Q000187:drug effects*; D013329:Structure-Activity Relationship; D014315:Triterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D000094042:Lupanes
D000962:Antimalarials; D005227:Fatty Acids; D053978:Pentacyclic Triterpenes; D014315:Triterpenes; C010480:lupeol; D000094042:Lupanes