Relevant Interactions of Antimicrobial Iron Chelators and Membrane Models Revealed by Nuclear Magnetic Resonance and Molecular Dynamics Simulations

• Type: Article in International Scientific Journal
• Date: 2014

Authors

Joao T S Coimbra (Author) Other; Tania Moniz (Author) Other; Natercia F Bras (Author) Other; Galya Iyanova (Author) Other; Pedro A Fernandes (Author) FCUP; Maria J Ramos (Author) FCUP; Maria Rangel (Author) ICBAS

Journal

Title: Journal of Physical Chemistry B

Vol. 118

Pages: 14590-14601

ISSN: 1520-6106

Publisher: American Chemical Society

Indexing

ISI Web of Knowledge - 8 Citations

Scopus - 10 Citations

Scientific classification

FOS: Natural sciences > Chemical sciences

Other information

Authenticus ID: P-00A-3QT

DOI: 10.1021/jp509491p

Abstract (EN): 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 12