Different behavior of artemisinin and tetraoxane in the oxidative degradationof phospholipid

摘要

The reaction of trioxane and tetraoxane endoperoxides with unsaturated phospholipid 1 in the presenceof Fe(II) was investigated in the absence of oxygen by means of tandem ESI-MS analysis. The spectralanalyses for the reaction mixtures showed that artemisinin 2 with a trioxane structure gave no peakexcept that for the remaining intact phospholipid 1 (m/z 758.9), indicating that there was no structuralchange to 1. On other hand, the reaction mixture of 1 with tetraoxanes 3 and 4 afforded a number of newpeaks (m/z 620-850) that were presumably assigned to oxidative degradation products originating fromphospholipid 1. Since this reaction was completely inhibited by the addition of a phenolic antioxidant, theprocess was considered to involve some free radical species. The newly discovered marked differences inreactivity between the trioxane and the tetraoxanes possibly reflects their different anti-malarial mecha-nisms, and this reactivity may contribute to the classification of a number of anti-malarial endoperoxideswhose mode of action is based on phospholipid oxidation.