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Probing drug/lipid interactions at the molecular level represents an important challenge …


Biology Articles » Biophysics » Molecular Biophysics » Characterization of the Interactions between Fluoroquinolone Antibiotics and Lipids: a Multitechnique Approach

Abstract
- Characterization of the Interactions between Fluoroquinolone Antibiotics and Lipids: a Multitechnique Approach

Characterization of the Interactions between Fluoroquinolone Antibiotics and Lipids: a Multitechnique Approach

Hayet Bensikaddour *, Nathalie Fa *, Ingrid Burton {dagger}, Magali Deleu {ddagger}, Laurence Lins §, André Schanck ¶, Robert Brasseur ¶, Yves F. Dufrêne {dagger}, Erik Goormaghtigh || and Marie-Paule Mingeot-Leclercq *

* Université Catholique de Louvain, Faculty of Medicine, Unité de Pharmacologie Cellulaire et Moléculaire, Brussels, Belgium; {dagger} Université Catholique de Louvain, Faculty of Agronomy, Unité de Chimie des Interfaces, Louvain-la-Neuve, Belgium; {ddagger} Faculté Universitaire des Sciences Agronomiques de Gembloux, Unité de Chimie Biologique Industrielle, and § Centre de Biophysique Moléculaire Numérique, Faculté Universitaire des Sciences Agronomiques de Gembloux, Gembloux, Belgium; Université Catholique de Louvain, Louvain-la-Neuve, Faculty of Sciences, Unité de Chimie Structurale et des Mécanismes Réactionnels, Belgium; and || Université Libre de Bruxelles, Faculty of Sciences, Unité de Structure et Fonction des Membranes Biologiques, Brussels, Belgium

An Open Access Article : Biophysical Journal 94:3035-3046 (2008).

 

Abstract

Probing drug/lipid interactions at the molecular level representsan important challenge in pharmaceutical research and membranebiophysics. Previous studies showed differences in accumulationand intracellular activity between two fluoroquinolones, ciprofloxacinand moxifloxacin, that may actually result from their differentialsusceptibility to efflux by the ciprofloxacin transporter. Inview of the critical role of lipids for the drug cellular uptakeand differences observed for the two closely related fluoroquinolones,we investigated the interactions of these two antibiotics withlipids, using an array of complementary techniques. Moxifloxacininduced, to a greater extent than ciprofloxacin, an erosionof the DPPC domains in the DOPC fluid phase (atomic force microscopy)and a shift of the surface pressure-area isotherms of DOPC/DPPC/fluoroquinolonemonolayer toward lower area per molecule (Langmuir studies).These effects are related to a lower propensity of moxifloxacinto be released from lipid to aqueous phase (determined by phasetransfer studies and conformational analysis) and a marked decreaseof all-trans conformation of acyl-lipid chains of DPPC (determinedby ATR-FTIR) without increase of lipid disorder and change inthe tilt between the normal and the germanium surface (alsodetermined by ATR-FTIR). All together, differences of ciprofloxacinas compared to moxifloxacin in their interactions with lipidscould explain differences in their cellular accumulation andsusceptibility to efflux transporters.


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