Characterization of the interactions between fluoroquinolone antibiotics and lipids: a multitechnique approach
Hayet Bensikaddour 1, Nathalie Fa 1, Ingrid Burton 2, Magali Deleu 3, Laurence Lins 4, André Schanck 1, Robert Brasseur 3, Yves Dufrêne 1, Erik Goormaghtigh 5 and Marie-Paule Mingeot-Leclercq 1*
1 Université catholique de Louvain
2 Université catholique de louvain
3 Faculté des Sciences agronomiques de Gembloux
4 Université catholique de Gembloux
5 Université Libre de Bruxelles
* To whom correspondence should be addressed. E-mail: mingeot{at}facm.ucl.ac.be.
Submitted on June 15, 2007
Revised on July 12, 2007
Accepted on 3 October 2007
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Abstract |
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Probing drug:lipid interactions at the molecular level represents an important challenge in pharmaceutical research and membrane biophysics. Previous studies showed differences in accumulation and intracellular activity between two fluoroquinolones, ciprofloxacin and moxifloxacin, that may actually result from their differential susceptibility to efflux by the ciprofloxacin transporter [1]. In view of the critical role of lipids for the drug cellular uptake and differences observed for the two closely related fluoroquinolones, we investigated the interactions of these two antibiotics with lipids, using an array of complementary techniques. Moxifloxacin induced in a more extent than ciprofloxacin, an erosion of the DPPC domains in the DOPC fluid phase (AFM) and a shift of the surface pressure-area isotherms of DOPC:DPPC:Fluoroquinolone monolayer towards the lower area per molecule (Langmuir studies). These effects are related to a lower propensity of moxifloxaxin to be released from lipid to aqueous phase (phase transfer studies and conformational analysis) and a marked decrease of all-trans conformation of acyl lipid chains of DPPC (ATR-FTIR) without increase of lipid disorder and change in the tilt between the normal and the germanium surface (ATR-FTIR). All together, differences of ciprofloxacin as compared to moxifloxacin in their interactions with lipids could explain differences in their cellular accumulation and therefore their activity against intracellular bacteria.
Key Words:
AFM, ATR-FTIR, Fluoroquinolones, Langmuir, Lipids, Molecular modeling
