Different behavior of artemisinin and tetraoxane in the oxidative degradation of phospholipid.
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.
Graduate School of Natural Science and Technology, Okayama University, Okayama 700-8530, Japan.
Naokazu
N
Kumura
Hirotaka
H
Furukawa
Arnold N
AN
Onyango
Minoru
M
Izumi
Shuhei
S
Nakajima
Hideyuki
H
Ito
Tsutomu
T
Hatano
Hye-Sook
HS
Kim
Yusuke
Y
Wataya
Naomichi
N
Baba
D000962:Antimalarials / Q000737:chemistry* / Q000494:pharmacology; D037621:Artemisinins / Q000737:chemistry*; D007501:Iron / Q000737:chemistry; D015227:Lipid Peroxidation; D010713:Phosphatidylcholines / Q000032:analysis / Q000737:chemistry*; D011450:Prostaglandin Endoperoxides, Synthetic / Q000737:chemistry; D021241:Spectrometry, Mass, Electrospray Ionization; D045568:Tetraoxanes / Q000737:chemistry* / Q000494:pharmacology
D000962:Antimalarials; D037621:Artemisinins; D010713:Phosphatidylcholines; D011450:Prostaglandin Endoperoxides, Synthetic; D045568:Tetraoxanes; C055402:1-palmitoyl-2-linoleoylphosphatidylcholine; C031327:artemisinin; D007501:Iron