Effects of an antimalarial quinazoline derivative on human erythrocytes and on cell membrane molecular models

Yareli Rojas-Aguirre, Francisco Hernández-Luis, César Mendoza-Martínez, Carlos Patricio Sotomayor, Luis Felipe Aguilar, Fernando Villena, Ivan Castillo, David J. Hernández, Mario Suwalsky

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24 Scopus citations


Plasmodium, the parasite which causes malaria in humans multiplies in the liver and then infects circulating erythrocytes. Thus, the role of the erythrocyte cell membrane in antimalarial drug activity and resistance has key importance. The effects of the antiplasmodial N 6-(4-methoxybenzyl) quinazoline-2,4,6-triamine (M4), and its inclusion complex (M4/HPβCD) with 2-hydroxypropyl-β-cyclodextrin (HPβCD) on human erythrocytes and on cell membrane molecular models are herein reported. This work evidences that M4/HPβCD interacts with red cells as follows: a) in scanning electron microscopy (SEM) studies on human erythrocytes induced shape changes at a 10 μM concentration; b) in isolated unsealed human erythrocyte membranes (IUM) a concentration as low as 1 μM induced sharp DPH fluorescence anisotropy decrease whereas increasing concentrations produced a monotonically decrease of DPH fluorescence lifetime at 37°C; c) X-ray diffraction studies showed that 200 μM induced a complete structural perturbation of dimyristoylphosphatidylcholine (DMPC) bilayers whereas no significant effects were detected in dimyristoylphosphatidylethanolamine (DMPE) bilayers, classes of lipids present in the outer and inner monolayers of the human erythrocyte membrane, respectively; d) fluorescence spectroscopy data showed that increasing concentrations of the complex interacted with the deep hydrophobic core of DMPC large unilamellar vesicles (LUV) at 18°C. All these experiments are consistent with the insertion of M4/HPβCD in the outer monolayer of the human erythrocyte membrane; thus, it can be considered a promising and novel antimalarial agent.

Original languageEnglish
Pages (from-to)738-746
Number of pages9
JournalBiochimica et Biophysica Acta - Biomembranes
Issue number3
StatePublished - Mar 2012


  • Cyclodextrin
  • Drug-membrane interaction
  • Erythrocyte membrane
  • Inclusion complex
  • Malaria
  • Quinazoline derivative


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