Isolation and antimalarial activity of new morphinan alkaloids on Plasmodium yoelii liver stage.
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.
Carraz
Maëlle
M
MNHN, USM 0502, CNRS, UMR 5154, Laboratoire de Chimie et Biochimie des Substances Naturelles, Muséum National d'Histoire Naturelle, 75005 Paris, France. maelle_carraz@yahoo.fr
Jossang
Akino
A
Rasoanaivo
Philippe
P
Mazier
Dominique
D
Frappier
François
F
D000818:Animals; D000962:Antimalarials / Q000302:isolation & purification* / Q000494:pharmacology; D002478:Cells, Cultured; D022781:Hepatocytes / Q000187:drug effects / Q000469:parasitology; D008109:Liver Diseases, Parasitic / Q000469:parasitology / Q000473:pathology / Q000517:prevention & control*; D029583:Menispermaceae / Q000737:chemistry; D051379:Mice; D009019:Morphinans / Q000302:isolation & purification* / Q000494:pharmacology; D024301:Plant Bark / Q000737:chemistry; D010946:Plants, Medicinal / Q000737:chemistry / Q000469:parasitology; D010967:Plasmodium yoelii / Q000187:drug effects* / Q000254:growth & development*
D000962:Antimalarials; D009019:Morphinans; C517160:tazopsine; C099120:sinococuline