Relevant
Interactions of Antimicrobial Iron Chelators
and Membrane Models Revealed by Nuclear Magnetic Resonance and Molecular
Dynamics Simulations
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Abstract
The
dynamics and interaction of 3-hydroxy-4-pyridinone fluorescent
iron chelators, exhibiting antimicrobial properties, with biological
membranes were evaluated through NMR and molecular dynamics simulations.
Both NMR and MD simulation results support a strong interaction of
the chelators with the lipid bilayers that seems to be strengthened
for the rhodamine containing compounds, in particular for compounds
that include ethyl groups and a thiourea link. For the latter type
of compounds the interaction reaches the hydrophobic core of the lipid
bilayer. The molecular docking and MD simulations performed for the
potential interaction of the chelators with DC-SIGN receptors provide
valuable information regarding the cellular uptake of these compounds
since the results show that the fluorophore fragment of the molecular
framework is essential for an efficient binding. Putting together
our previous and present results, we put forward the hypothesis that
all the studied fluorescent chelators have access to the cell, their
uptake occurs through different pathways and their permeation properties
correlate with a better access to the cell and its compartments and,
consequently, with the chelators antimicrobial properties