1: Biophys J. 2008 Apr 15;94(8):3035-46. Epub 2008 Jan 4.

Characterization of the interactions between fluoroquinolone antibiotics and
lipids: a multitechnique approach.

Bensikaddour H, Fa N, Burton I, Deleu M, Lins L, Schanck A, Brasseur R, Dufrêne
YF, Goormaghtigh E, Mingeot-Leclercq MP.

Université Catholique de Louvain, Faculty of Medicine, Unité de Pharmacologie
Cellulaire et Moléculaire, Brussels, Belgium.

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. 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, to a greater extent than
ciprofloxacin, an erosion of the DPPC domains in the DOPC fluid phase (atomic
force microscopy) and a shift of the surface pressure-area isotherms of
DOPC/DPPC/fluoroquinolone monolayer toward lower area per molecule (Langmuir
studies). These effects are related to a lower propensity of moxifloxacin to be
released from lipid to aqueous phase (determined by phase transfer studies and
conformational analysis) and a marked decrease of all-trans conformation of
acyl-lipid chains of DPPC (determined by ATR-FTIR) without increase of lipid
disorder and change in the tilt between the normal and the germanium surface
(also determined by ATR-FTIR). All together, differences of ciprofloxacin as
compared to moxifloxacin in their interactions with lipids could explain
differences in their cellular accumulation and susceptibility to efflux

PMID: 18178657 [PubMed - in process]

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