Antimalarial Activity of Simalikalactone E, a New Quassinoid from Quassia amara L. (Simaroubaceae)
Antimalarial Activity of Simalikalactone E, a New Quassinoid from Quassia amara L. (Simaroubaceae)
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DOI：
10.1128/aac.00951-09
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发表时间：
2009-10-01
影响因子：
4.9
通讯作者：
Jullian, V.
中科院分区：
文献类型：
--
作者：
Cachet, N.;Hoakwie, F.;Jullian, V.
本文报道了一种新的苦木素类化合物的分离和鉴定，命名为西马阿马拉E（SkE）。（Simaroubaceae）叶。这种新的分子抑制恶性疟原虫在体外培养的50%，在浓度范围从24至68 nM，独立的菌株对氯喹的敏感性的生长。我们还表明，该化合物能够减少配子体血症，其50%抑制浓度比伯氨喹低7倍。SkE的毒性低于另一种抗疟苦木素类化合物Simalikalactone D（SkD）。阿马拉，其对哺乳动物细胞的细胞毒性依赖于细胞系，当在非肿瘤细胞上测试时显示出良好的选择性指数。在体内，SkE抑制鼠疟原虫vinckei petteri 50%的增长，在1和0.5毫克/公斤体重/天，通过口服或腹腔途径，分别。因此，需要重新考虑类苦木素作为抗疟分子来源的贡献。
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.