Antimalarial activity of simalikalactone E, a new quassinoid from quassia amara L (simaroubaceae)

N. Cachet (1) , Franciane Hoakwie (1) , Stéphanie Bertani (2) , Geneviève Bourdy (1) , Eric Deharo (1) , Didier Stien (3) , Emeline Houël (3) , Heinz Gornitzka (4) , Judith Fillaux (5) , S. Chevalley (1) , Alexis Valentin (1) , V. Jullian (1)

1 Pharmacochimie des substances naturelles et pharmacophores redox
2 PHARMA-DEV - Pharmacochimie et Biologie pour le Développement
3 ECOFOG - Ecologie des forêts de Guyane
4 LCC - Laboratoire de chimie de coordination
5 Service de Parasitologie et Mycologie [CHU Toulouse]

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.

Domaines: Chimie thérapeutique; Parasitologie

N. Cachet, Franciane Hoakwie, Stéphanie Bertani, Geneviève Bourdy, Eric Deharo, et al.. Antimalarial activity of simalikalactone E, a new quassinoid from quassia amara L (simaroubaceae). Antimicrobial Agents and Chemotherapy, 2009, 53 (10), pp.4393-4398. ⟨10.1128/AAC.00951-09⟩. ⟨hal-01032126⟩