A nuclear magnetic resonance study of the interactions of the antimalarials chloroquine, quinacrine, quinine and mefloquine with lipids extracted from normal human erythrocytes.
The interaction of four antimalarials (chloroquine, quinacrine, mefloquine and quinine) with lipid membranes re-formed from lipid extracts of normal human erythrocytes was studied using 2H- and lipid extracts of normal human erythrocytes was studied using 2H- and 31P-nuclear magnetic resonance (NMR). Inclusion of small amounts of chain-perdeuterated dipalmitoylphosphatidylcholine (DPPC) or dipalmitoylphosphatidylethanolamine (DPPE) as an 2H-NMR probe allowed us to study separately the effects of drugs on PC or PE components of the membranes. Only a very small decrease in the order parameters of the DPPE, but not the DPPC probe, was observed in the presence of chloroquine at a molar ratio of 1:5 of drug to lipid. Addition of quinacrine at the same molar ratio resulted in a small but significant decrease in the order parameters of the lipid side chains; identical effects were obtained with DPPC or DPPE perdeuterated probes. The presence of quinacrine did not induce non-bilayer lipid phases. In contrast, mefloquine and quinine produced a significant disordering of the lipid side chains; the effect was considerably larger with the DPPE probe. In addition, both mefloquine and quinine induced non-bilayer phases of the lipids; mefloquine induced formation of hexagonal and micellar lipid conformation, whereas addition of quinine resulted in the formation of lipid micelles only. The lipid polymorphism induced by either of these drugs was more pronounced when the DPPE component was observed, indicating that the non-bilayer phases were enriched in PE. The results suggest the presence of strong interactions between mefloquine and quinine with lipid bilayers, especially with the PE component.(ABSTRACT TRUNCATED AT 250 WORDS)
Zidovetzki
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R
Department of Biology, University of California, Riverside 92521.
Sherman
I W
IW
Maguire
P A
PA
De Boeck
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H
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000378:metabolism; D000962:Antimalarials / Q000378:metabolism* / Q000494:pharmacology; D002738:Chloroquine / Q000378:metabolism; D003903:Deuterium; D004912:Erythrocytes / Q000032:analysis; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D015767:Mefloquine / Q000378:metabolism; D008563:Membrane Lipids / Q000302:isolation & purification / Q000378:metabolism*; D010714:Phosphatidylethanolamines / Q000378:metabolism; D010759:Phosphorus Isotopes; D011796:Quinacrine / Q000378:metabolism; D011803:Quinine / Q000378:metabolism
D000962:Antimalarials; D008563:Membrane Lipids; D010714:Phosphatidylethanolamines; D010759:Phosphorus Isotopes; D015060:1,2-Dipalmitoylphosphatidylcholine; C007510:1,2-dipalmitoyl-3-phosphatidylethanolamine; D002738:Chloroquine; D011803:Quinine; D003903:Deuterium; D011796:Quinacrine; D015767:Mefloquine