Interaction of Quinine with Model Lipid Membranes of Different Compositions

Porcar, Iolanda; Codoñer, Armando; Gómez, Clara M.; Abad, Concepción; Campos, Agustı́n

doi:10.1002/jps.10254

Cited by 21 publications

(17 citation statements)

References 34 publications

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“…Positively charged drugs have been shown to interact stronger with liposomes containing larger PS content (37). This is consistent with other literature reports, for example, greater DMPG content in membranes also resulted in an increase in the degree of binding of Quinine to lipid membranes (33). Liposomes consisting of 30% PS had an affinity for the positively charged drug, flurazepam of about 4.8 times that of membranes consisting of PC only, determined using second derivative spectrophotometry (38).…”

Section: Effect Of Liposome Compositionsupporting

confidence: 86%

“…The decrease in partitioning with increase in ionic strength or increase in buffer concentration is consistent with previous determinations (33). This reduced interaction is due to the shielding of the charge on the liposome surface in addition to the shielding of the charge on the drug molecule by the buffer counter ions, thus decreasing the electrostatic interactions.…”

Section: Effect Of Buffer Concentrationsupporting

confidence: 86%

“…This would also explain the lack of difference in partitioning with the neutral solutes as the buffer is varied since they have no electrostatic interactions. A stronger effect of the ionic strength has been observed when more anionic vesicles are used (33).…”

Section: Effect Of Buffer Concentrationmentioning

confidence: 96%

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Interaction of Basic Drugs with Lipid Bilayers Using Liposome Electrokinetic Chromatography

Carrozzino

Khaledi

2004

Pharm Res

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These studies demonstrate the overall buffer ionic strength at a given pH is more important than buffer type and concentration. The interaction of positively charged drugs with charged lipid bilayer membranes is selectively influenced by the pKa of the drug. Liposomes are more biologically relevant in vitro models for cell membranes than octanol, and LEKC provides a unique combination of advantages for rapid screening of drug-membrane interactions.

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Section: Effect Of Liposome Compositionsupporting

confidence: 86%

Section: Effect Of Buffer Concentrationsupporting

confidence: 86%

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Interaction of Basic Drugs with Lipid Bilayers Using Liposome Electrokinetic Chromatography

Carrozzino

Khaledi

2004

Pharm Res

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“…The quinoline-methanols MFQ and QN are known to bind with high affinity to membrane and purified phospholipids, suggesting that these molecules may indeed be biological targets [62]–[66]. These drugs are thought to exert their antimalarial effects by impairing membrane recycling within the endo-lysosomal system of the intracellular parasite [67]–[69], ultimately blocking heme degradation and causing death.…”

Section: Discussionmentioning

confidence: 99%

Genome Wide Adaptations of Plasmodium falciparum in Response to Lumefantrine Selective Drug Pressure

et al. 2012

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The combination therapy of the Artemisinin-derivative Artemether (ART) with Lumefantrine (LM) (Coartem®) is an important malaria treatment regimen in many endemic countries. Resistance to Artemisinin has already been reported, and it is feared that LM resistance (LMR) could also evolve quickly. Therefore molecular markers which can be used to track Coartem® efficacy are urgently needed. Often, stable resistance arises from initial, unstable phenotypes that can be identified in vitro. Here we have used the Plasmodium falciparum multidrug resistant reference strain V1S to induce LMR in vitro by culturing the parasite under continuous drug pressure for 16 months. The initial IC50 (inhibitory concentration that kills 50% of the parasite population) was 24 nM. The resulting resistant strain V1SLM, obtained after culture for an estimated 166 cycles under LM pressure, grew steadily in 378 nM of LM, corresponding to 15 times the IC50 of the parental strain. However, after two weeks of culturing V1SLM in drug-free medium, the IC50 returned to that of the initial, parental strain V1S. This transient drug tolerance was associated with major changes in gene expression profiles: using the PFSANGER Affymetrix custom array, we identified 184 differentially expressed genes in V1SLM. Among those are 18 known and putative transporters including the multidrug resistance gene 1 (pfmdr1), the multidrug resistance associated protein and the V-type H+ pumping pyrophosphatase 2 (pfvp2) as well as genes associated with fatty acid metabolism. In addition we detected a clear selective advantage provided by two genomic loci in parasites grown under LM drug pressure, suggesting that all, or some of those genes contribute to development of LM tolerance – they may prove useful as molecular markers to monitor P. falciparum LM susceptibility.

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“…Quinine accumulation by erythrocytes infected with malaria parasites has received little study (Polet and Barr, 1968). There is ample evidence, however, that quinine binds to phospholipids Demel, 1983, 1984;Porcar et al, 2003).…”

Section: Evidence Of a Quinoline Drug Target In Addition To Fpmentioning

confidence: 97%

Ferriprotoporphyrin IX, phospholipids, and the antimalarial actions of quinoline drugs

2004

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Interaction of Quinine with Model Lipid Membranes of Different Compositions

Cited by 21 publications

References 34 publications

Interaction of Basic Drugs with Lipid Bilayers Using Liposome Electrokinetic Chromatography

Interaction of Basic Drugs with Lipid Bilayers Using Liposome Electrokinetic Chromatography

Genome Wide Adaptations of Plasmodium falciparum in Response to Lumefantrine Selective Drug Pressure

Ferriprotoporphyrin IX, phospholipids, and the antimalarial actions of quinoline drugs

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