title: Relevant interactions of antimicrobial iron chelators and membrane models revealed by nuclear magnetic resonance and molecular dynamics simulations.
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.
authors.affiliation: REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto , Rua do Campo Alegre s/n, 4169-007 Porto, Portugal.
authors.forename: João T S
authors.initials: JT
authors.lastname: Coimbra
authors.forename: Tânia
authors.initials: T
authors.lastname: Moniz
authors.forename: Natércia F
authors.initials: NF
authors.lastname: Brás
authors.forename: Galya
authors.initials: G
authors.lastname: Ivanova
authors.forename: Pedro A
authors.initials: PA
authors.lastname: Fernandes
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Ramos
authors.forename: Maria
authors.initials: M
authors.lastname: Rangel
mesh_terms: D000890:Anti-Infective Agents / Q000737:chemistry*; D015815:Cell Adhesion Molecules / Q000737:chemistry* / Q000378:metabolism; D002462:Cell Membrane / Q000737:chemistry* / Q000378:metabolism; D007502:Iron Chelating Agents / Q000737:chemistry* / Q000378:metabolism; D037181:Lectins, C-Type / Q000737:chemistry* / Q000378:metabolism; D008051:Lipid Bilayers / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D056004:Molecular Dynamics Simulation; D011487:Protein Conformation; D011728:Pyridones / Q000737:chemistry / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000737:chemistry* / Q000378:metabolism; D012235:Rhodamines / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D000890:Anti-Infective Agents; D015815:Cell Adhesion Molecules; D007502:Iron Chelating Agents; D037181:Lectins, C-Type; D008051:Lipid Bilayers; D011728:Pyridones; D011956:Receptors, Cell Surface; D012235:Rhodamines; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C000600710:MRB7 compound; C000600711:MRB8 compound; C020366:3-hydroxy-4-pyridone