Different behavior of artemisinin and tetraoxane in the oxidative degradation of phospholipid

• Published in: Chemistry and physics of lipids 2009-08, Vol.160 (2), p.114-120
• Main Authors: Kumura, Naokazu, Furukawa, Hirotaka, Onyango, Arnold N., Izumi, Minoru, Nakajima, Shuhei, Ito, Hideyuki, Hatano, Tsutomu, Kim, Hye-Sook, Wataya, Yusuke, Baba, Naomichi
• Format: Article
• Language: English
• Subjects: Antimalarials - chemistry; Antimalarials - pharmacology; Artemisinin; Artemisinins - chemistry; Endoperoxide; Iron - chemistry; Lipid Peroxidation; Phosphatidylcholines - analysis; Phosphatidylcholines - chemistry; Phospholipid; Prostaglandin Endoperoxides, Synthetic - chemistry; Reactive oxygen species; Spectrometry, Mass, Electrospray Ionization; Tetraoxane; Tetraoxanes - chemistry; Tetraoxanes - pharmacology
• ISSN: 0009-3084; 1873-2941
• DOI: 10.1016/j.chemphyslip.2009.04.005

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