Tuning the Anti(myco)bacterial Activity of 3-Hydroxy-4-pyridinone Chelators through Fluorophores.
TLDR
A critical account of the entire work in the design of chelators to address Mycobacterium avium infections is given and the statement “to label means to change” is justified.Abstract:
Controlling the sources of Fe available to pathogens is one of the possible strategies that can be successfully used by novel antibacterial drugs. We focused our interest on the design of chelators to address Mycobacterium avium infections. Taking into account the molecular structure of mycobacterial siderophores and considering that new chelators must be able to compete for Fe(III), we selected ligands of the 3-hydroxy-4-pyridinone class to achieve our purpose. After choosing the type of chelating unit it was also our objective to design chelators that could be monitored inside the cell and for that reason we designed chelators that could be functionalized with fluorophores. We didn’t realize at the time that the incorporation a fluorophore, to allow spectroscopic detection, would be so relevant for the antimycobacterial effect or to determine the affinity of the chelators towards biological membranes. From a biophysical perspective, this is a fascinating illustration of the fact that functionalization of a molecule with a particular label may lead to a change in its membrane permeation properties and result in a dramatic change in biological activity. For that reason we believe it is interesting to give a critical account of our entire work in this area and justify the statement “to label means to change”. New perspectives regarding combined therapeutic approaches and the use of rhodamine B conjugates to target closely related problems such as bacterial resistance and biofilm production are also discussed.read more
Citations
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New strong extrafunctionalizable tris(3,4-HP) and bis(3,4-HP) metal sequestering agents: synthesis, solution and in vivo metal chelation
Valeria Marina Nurchi,Rosita Cappai,Rosita Cappai,Karam Chand,Sílvia Chaves,Lurdes Gano,Guido Crisponi,Massimiliano Francesco Peana,M. Antonietta Zoroddu,M. Amélia Santos +9 more
TL;DR: Their chelating capacity towards Fe and Al was evaluated in aqueous solution, by potentiometric and spectroscopic techniques, and they proved to be strong sequestering agents for these metal ions without depletion of Zn, an essential biometal.
Journal ArticleDOI
Iron as Therapeutic Target in Human Diseases.
TL;DR: Iron is essential for almost all organisms, being involved in oxygen transport, DNA synthesis, and respiration; however, it is also potentially toxic via the formation of free radicals.
Journal ArticleDOI
Polyglycerol-Based Macromolecular Iron Chelator Adjuvants for Antibiotics To Treat Drug-Resistant Bacteria.
TL;DR: Macromolecular iron chelators, conjugates of a high affinity iron chelator with polyglycerol, are developed in an attempt to sequester iron-uptake by bacteria to limit their growth in order to enhance antibiotic activity.
References
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