Antimalarial activity of simalikalactone E, a new quassinoid from Quassia amara L. (Simaroubaceae).
We report the isolation and identification of a new quassinoid named simalikalactone E (SkE), extracted from a widely used Amazonian antimalarial remedy made out of Quassia amara L. (Simaroubaceae) leaves. This new molecule inhibited the growth of Plasmodium falciparum cultured in vitro by 50%, in the concentration range from 24 to 68 nM, independently of the strain sensitivity to chloroquine. We also showed that this compound was able to decrease gametocytemia with a 50% inhibitory concentration sevenfold lower than that of primaquine. SkE was found to be less toxic than simalikalactone D (SkD), another antimalarial quassinoid from Q. amara, and its cytotoxicity on mammalian cells was dependent on the cell line, displaying a good selectivity index when tested on nontumorogenic cells. In vivo, SkE inhibited murine malaria growth of Plasmodium vinckei petteri by 50% at 1 and 0.5 mg/kg of body weight/day, by the oral or intraperitoneal routes, respectively. The contribution of quassinoids as a source of antimalarial molecules needs therefore to be reconsidered.
Cachet
N
N
Laboratoire de Pharmacochimie des Substances Naturelles et Pharmacophores Redox, UMR 152, UPS, Université de Toulouse, 118 Route de Narbonne, F-31062 Toulouse Cedex 9, France.
Hoakwie
F
F
Bertani
S
S
Bourdy
G
G
Deharo
E
E
Stien
D
D
Houel
E
E
Gornitzka
H
H
Fillaux
J
J
Chevalley
S
S
Valentin
A
A
Jullian
V
V
D000818:Animals; D000962:Antimalarials / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008288:Malaria / Q000188:drug therapy / Q000469:parasitology; D015394:Molecular Structure; D010963:Plasmodium falciparum / Q000187:drug effects*; D036702:Quassins / Q000737:chemistry / Q000494:pharmacology*; D029641:Simaroubaceae / Q000737:chemistry*; D014709:Vero Cells
D000962:Antimalarials; D036702:Quassins