New clerodane diterpenoids from Laetia procera (Poepp.) Eichler (Flacourtiaceae), with antiplasmodial and antileishmanial activities.
Extracts of Laetia procera (Flacourtiaceae) displayed significant in vitro activity against Plasmodium falciparum. P. falciparum bioassay guided fractionation of a trunk bark extract of this plant led to the isolation of six clerodane diterpenoids (1-6) and a butanolide (7). Five of these compounds are new and called Laetiaprocerine A-D (3-6) and Laetianolide A (7). Their structures were established on the basis of 1D and 2D NMR experiments. Absolute configurations of 1 and 2 were determined by a modified Mosher's method and the absolute configuration of 5 by chemical correlation. The clerodane diterpenoids displayed activities against P. falciparum with an IC50 down to 0.5 microM on FCb1 and F32 strains, and also cytotoxicity toward human tumor cell line MCF7. The most active compound showed a selectivity index of 6.8. Some of these compounds also displayed activities against Leishmania amazonensis amastigote axenic stages and promastigote.
Jullian
Valérie
V
UMR 152 (IRD-UPS) Institut de Recherche pour le Développement-Université Paul Sabatier, Faculté de Pharmacie, 35 chemin des Maraîchers, 31062 Toulouse cedex 04, France. jullian@cict.fr
Bonduelle
Colin
C
Valentin
Alexis
A
Acebey
Lucia
L
Duigou
Anne-Gaëlle
AG
Prévost
Marie-Francoise
MF
Sauvain
Michel
M
D000818:Animals; D000962:Antimalarials / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004224:Diterpenes / Q000737:chemistry*; D045785:Diterpenes, Clerodane / Q000737:chemistry*; D006801:Humans; D020128:Inhibitory Concentration 50; D007891:Leishmania / Q000187:drug effects*; D009682:Magnetic Resonance Spectroscopy; D031566:Magnolia / Q000737:chemistry*; D015394:Molecular Structure; D010963:Plasmodium falciparum / Q000187:drug effects*; D013329:Structure-Activity Relationship
D000962:Antimalarials; D004224:Diterpenes; D045785:Diterpenes, Clerodane