新型吗啡喃生物碱对约氏疟原虫肝期的分离及其抗疟活性

Isolation and antimalarial activity of new morphinan alkaloids on Plasmodium yoelii liver stage.

作者信息

Carraz Maëlle, Jossang Akino, Rasoanaivo Philippe, Mazier Dominique, Frappier François

机构信息

MNHN, USM 0502, CNRS, UMR 5154, Laboratoire de Chimie et Biochimie des Substances Naturelles, Muséum National d'Histoire Naturelle, 75005 Paris, France.

出版信息

Bioorg Med Chem. 2008 Jun 1;16(11):6186-92. doi: 10.1016/j.bmc.2008.04.033. Epub 2008 Apr 18.

DOI:10.1016/j.bmc.2008.04.033

PMID:18456502

Abstract

Decoction of Strychnopsis thouarsii is used in the Malagasy traditional medicine to combat malaria. We have shown that this traditional remedy prevents malaria infection by targeting Plasmodium at its early liver stage. Bioassay-guided fractionation of S. thouarsii stem barks extracts, using a rodent Plasmodium yoelii liver stage parasites inhibition assay, led to isolate the new morphinan alkaloid tazopsine (1) together with sinococuline (2) and two other new related morphinan analogs, 10-epi-tazopsine (3) and 10-epi-tazoside (4). Structures were characterized by 2D NMR, MS, and CD spectral analysis. Compounds 1-3 were found to fully inhibit the rodent P. yoelii liver stage parasites in vitro.

摘要

马达加斯加传统医学中使用马岛天仙煎剂来对抗疟疾。我们已经表明，这种传统药物通过在疟原虫早期肝脏阶段靶向疟原虫来预防疟疾感染。使用啮齿动物约氏疟原虫肝脏阶段寄生虫抑制试验，对马岛天仙茎皮提取物进行生物测定指导的分级分离，导致分离出新型吗啡喃生物碱塔佐平（1）以及华千金藤碱（2）和另外两种新的相关吗啡喃类似物，10-表塔佐平（3）和10-表塔佐苷（4）。通过二维核磁共振、质谱和圆二色光谱分析对结构进行了表征。发现化合物1-3在体外能完全抑制啮齿动物约氏疟原虫肝脏阶段的寄生虫。