Interaction of the Antimalarial Agents Halofantrine and Lumefantrine with Lipid Bilayers

• Published in: Chemical & pharmaceutical bulletin Vol. 51; no. 3; pp. 241 - 246
• Main Authors: Go, Mei-Lin, Li, Qiu-Tian
• Format: Journal Article
• Language: English
• Published: Tokyo The Pharmaceutical Society of Japan 01.03.2003; Maruzen; Japan Science and Technology Agency
• Subjects: 1,2-Dipalmitoylphosphatidylcholine - metabolism; Animals; Antibiotics. Antiinfectious agents. Antiparasitic agents; antimalarial agent; Antimalarials - chemistry; Antimalarials - metabolism; Antiparasitic agents; Biological and medical sciences; diphenylhexatriene; Erythrocyte Membrane - metabolism; Ethanolamines - chemistry; Ethanolamines - metabolism; Fluorenes - chemistry; Fluorenes - metabolism; fluorescence anisotropy; halofantrine; lipid bilayer organisation; Lipid Bilayers - metabolism; Lumefantrine; Male; Medical sciences; Mice; Pharmacology. Drug treatments; Phenanthrenes - chemistry; Phenanthrenes - metabolism; Phosphatidylcholines - metabolism; Antimalarial; Phospholipid; Molecular interaction; Halofantrine; Antiprotozoal agent; diphenylhexatriene; antimalarial agent; fluorescence anisotropy; Parasiticid; lipid bilayer organisation; Fluorescence polarization; Rodentia; Red blood cell; Permeability; Complex lipid; Bilayer; Optical anisotropy; Vertebrata; Biological fixation; Mammalia; Mouse; Animal; Plasma membrane; Phosphatidylcholine; Lumefantrine
• ISSN: 0009-2363; 1347-5223
• DOI: 10.1248/cpb.51.241

The effects of antimalarial drugs halofantrine and lumefantrine on the fluoresence anisotropy of diphenylhexatriene (DPH)-containing phospholipid vesicles have been examined. Lumefantrine increases DPH anisotropy, indicating a condensing effect on bilayers of dipalmitoylphosphatidyl choline (DPPC), dioleoylphosphatidylcholine (DOPC), egg lecithin and mouse erythrocyte membranes (including membranes isolated from plasmodial-infected mice). Its condensing effect is more pronounced in bilayers of lower microviscosity. In contrast, increases or decreases in DPH anisotropy are observed with halofantrine, depending on the nature of the lipid. Decreases in anisotropy, which reflect a perturbing effect, are observed in bilayers of high microviscosity (for example, gel state of DPPC bilayers). Increases in anisotropy are observed in bilayers of low microviscosity (such as DOPC and egg lecithin bilayers). The perturbing effect of halofantrine is further confirmed by the increases in permeability of calcein-containing DPPC vesicles in the presence of the drug. However the perturbative effects of halofantrine are observed to the same magnitude in uninfected and plasmodial-infected erythrocyte membranes, and may not be relevant to the antimalarial action of the drug. In contrast, the condensing effect of lumefantrine is significantly greater in infected erythrocyte membranes and may contribute to its antimalarial action.