title: New findings on Simalikalactone D, an antimalarial compound from Quassia amara L. (Simaroubaceae).
abstract: Quassia amara L. (Simaroubaceae) is a species widely used as tonic and is claimed to be an efficient antimalarial all over the Northern part of the Amazon basin. Quassinoid compound Simalikalactone D (SkD) has been shown to be one of the molecules responsible for the antiplasmodial activity of a watery preparation made out of juvenile fresh leaves of this plant. Because of its strong antimalarial activity, we decided to have a further insight of SkD pharmacological properties, alone or in association with classical antimalarials. At concentrations of up to 200μM, we showed herein that SkD did not exert any apoptotic or necrotic activities in vitro on lymphoblastic cells. However, an antiproliferative effect was evident at concentrations higher than 45nM. SkD was inefficient at inhibiting heme biomineralization and the new permeability pathways induced by the parasite in the host erythrocyte membrane. With respect to Plasmodium falciparum erythrocytic stages, SkD was almost inactive on earlier and later parasite stages, but potently active at the 30th h of parasite cycle when DNA replicates in mature trophozoites. In vitro combination studies with conventional antimalarial drugs showed that SkD synergizes with atovaquone (ATO). The activity of ATO on the Plasmodium mitochondrial membrane potential was enhanced by SkD, which on its own had a poor effect on this cellular parameter.
authors.affiliation: USM0307, Laboratoire de Parasitologie Comparée et Modèles Expérimentaux, Muséum National d'Histoire Naturelle (MNHN), Paris, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Bertani
authors.forename: Emeline
authors.initials: E
authors.lastname: Houël
authors.forename: Valérie
authors.initials: V
authors.lastname: Jullian
authors.forename: Geneviève
authors.initials: G
authors.lastname: Bourdy
authors.forename: Alexis
authors.initials: A
authors.lastname: Valentin
authors.forename: Didier
authors.initials: D
authors.lastname: Stien
authors.forename: Eric
authors.initials: E
authors.lastname: Deharo
mesh_terms: D000962:Antimalarials / Q000494:pharmacology*; D002460:Cell Line / Q000187:drug effects; D002463:Cell Membrane Permeability / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004910:Erythrocyte Membrane / Q000187:drug effects / Q000378:metabolism; D004912:Erythrocytes / Q000187:drug effects / Q000469:parasitology; D006418:Heme / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D010936:Plant Extracts / Q000494:pharmacology; D018515:Plant Leaves / Q000737:chemistry; D010963:Plasmodium falciparum / Q000187:drug effects*; D010967:Plasmodium yoelii / Q000187:drug effects*; D032271:Quassia / Q000737:chemistry*; D036702:Quassins / Q000494:pharmacology*
chemical_list: D000962:Antimalarials; D010936:Plant Extracts; D036702:Quassins; C024970:simalikalactone D; D006418:Heme