The diversity and utility of arylthiazoline and aryloxazoline siderophores: Challenges of coordination chemistry, biological activity and selected applications

One of the factors necessary for the survivability and growth of microorganisms are iron ions. For the uptake of this vital metal ion from the surrounding environment, microorganisms have evolved a system which employs low-molecular mass, high-affinity chelators called siderophores. Bacteria and fungi rely on this system especially during infections, and siderophores are considered as a major virulence factor. Siderophores characteristics, role and acquisition mechanisms have been the subject of many authoritative and insightful reviews, however, arylthiazoline and aryloxazoline-type siderophores are rarely discussed together as a separate category of compounds. Reviewing those compounds side by side provides a unique possibility to notice the subtle structural differences which are greatly influencing their biological activity. By collecting a vast amount of data and presenting it together with insightful discussion, the authors are providing an aid in understanding the relationship between the structure of siderophores and their functions. The discussion involves the coordination properties of siderophores towards Fe(III), as well as importance of their structural fine-tuning, recognition mechanisms by outer membrane transporters (OMTs) and periplasmic substrate-binding proteins (SBPs) involved in siderophore uptake, as well as their transport under changing physiological conditions. The uncanonical role of siderophores in biological systems is also discussed, as their capability to bind non-iron metal ions is a subject of numerous ongoing research and draws increasing attention of the scientific world. The last section presents the great therapeutical potential of discussed siderophores and their recognition machineries employed as components of vaccine formulations or an attractive spot for targeted pharmaceuticals and vectorization of antimicrobial or imaging agents.