Host-Guest Interactions Between Betacyclodextrin And Selected Fluoroquinolones: A Molecular Modelling Study
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Date
2016-03
Authors
Mousa Al-Wahsh, Saleh Ahmad
Journal Title
Journal ISSN
Volume Title
Publisher
Universiti Sains Malaysia
Abstract
Fluoroquinolones (FQs) is an important group of antibiotics made up of a
hydrophobic quinolone and a hydrophilic piperazine rings. Beta-cyclodextrin (β-CD)
and its derivatives are currently being widely used in drug delivery systems, owing to
its hydrophobic cavities which are capable of forming inclusion complexes with a
variety of organic molecules. In this work, the host-guest interactions between FQs
and β-CD were investigated using three molecular modelling techniques, i.e.
quantum mechanics, molecular docking and molecular dynamics. The penetration of
FQ molecules into the β-CD cavity take place via two orientations which are Aorientation
with the quinolone ring or C-orientation with the piperazine ring facing
towards the β-CD cavity. The effect of solvent was modeled implicitly using
polarizable continuum model (PCM) in the quantum mechanics calculation and by
simple point charge water model (SPC) in a 100 ps molecular dynamics simulation.
The quantum mechanics calculations show the inclusion of FQs into the β-CD cavity
occur via the piperazine ring and is 230-241 kJ/mol more favourable than via the
quinolone ring facing in. In the molecular docking simulation, the stability of the
inclusion complexes with varying number of H2O displaced from the β-CD cavity
influenced the fitting of the FQ molecule into the β-CD’s cavity. In molecular
dynamics simulation, the effect of solvent on the conformational change of β-CD and
the movement of the FQ molecule inside and outside the cavity has been investigated
using the NPT ensemble.
Description
Keywords
Molecular