Hydroxyquinolines as iron chelators.
The interest in synthetic siderophore mimics includes therapeutic applications (iron chelation therapy), the design of more effective agents to deliver Fe to plants and the development of new chemical tools for studies of iron metabolism and for a better understanding of iron assimilation processes in living systems. The 8-hydroxyquinoline bidentate chelate moiety offers an alternative to the usual hydroxamic acid, catechol and/or alpha-hydroxycarboxylic acid metal-binding groups encountered in natural siderophores. The promising results obtained by the tris hydroxyquinoline-based ligand O-TRENSOX are summarized. O-TRENSOX exhibits a high and selective affinity for Fe(III) complexation. Its efficiency in delivering Fe to plants as well as its efficiency for iron mobilization, cellular protection and antiproliferative effects have been evidenced. Other chelators of the O-TRENSOX family (mixed catechol / 8-hydroxyquinoline ligands, lipophilic ligands) are also described. Some results question whether the use of partition coefficients is pertinent to foresee the activity of iron chelators. The development of probes (fluorescent, radioactive, spin labelled) based on the O-TRENSOX backbone is in progress. 8-hydroxyquinoline iron chelators seem to have a promising future.
Pierre
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JL
Laboratoire de Chimie Biomimétique, LEDSS, UMR CNRS 5616, Université J. Fourier, Grenoble, France. Jean.Louis.Pierre@ujf-grenoble.fr
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D000818:Animals; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D005021:Ethylamines / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D006912:Hydroxyquinolines / Q000737:chemistry / Q000494:pharmacology*; D007502:Iron Chelating Agents / Q000737:chemistry / Q000494:pharmacology*; D019190:Iron Overload / Q000188:drug therapy / Q000378:metabolism; D008024:Ligands
D005021:Ethylamines; D006912:Hydroxyquinolines; D007502:Iron Chelating Agents; D008024:Ligands; C097548:trensox