Prochelator strategies for site-selective activation of metal chelators.
Metal dyshomeostasis has been involved in the etiology of a host of pathologies such as Wilson's, Alzheimer's, Parkinson's, Huntington's, transfusion-related iron overload diseases and cancer. Although metal chelating agents represent a necessary therapeutic strategy in metal overload diseases, long-term use of strong chelators that are not selective, can be anticipated perturbing normal physiological functions of essential metal-requiring biomolecules. In this context, the last decade has seen a growing interest in the development of molecules, referred to as "prochelators", that have little affinity for metal ions until they are activated in response to specific stimuli. Here, we present the main strategies applied to develop safe prochelators and focus on chosen examples to provide an overview of this field to date.
Dipartimento di Scienze Chimiche, Università degli Studi di Catania, Viale A. Doria, 6, 95125 Catania, Italy; Consorzio Interuniversitario di Ricerca in Chimica dei Metalli nei Sistemi Biologici, C.I.R.C.M.S.B., Unità di Ricerca di Catania, 95125 Catania, Italy. Electronic address: oliveri.valentina22@gmail.com.
Valentina
V
Oliveri
Dipartimento di Scienze Chimiche, Università degli Studi di Catania, Viale A. Doria, 6, 95125 Catania, Italy; Consorzio Interuniversitario di Ricerca in Chimica dei Metalli nei Sistemi Biologici, C.I.R.C.M.S.B., Unità di Ricerca di Catania, 95125 Catania, Italy.
Graziella
G
Vecchio
D002614:Chelating Agents / Q000737:chemistry* / Q000378:metabolism / Q000627:therapeutic use; D003300:Copper / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000737:chemistry / Q000378:metabolism; D006867:Hydrolases / Q000737:chemistry / Q000378:metabolism; D006912:Hydroxyquinolines / Q000737:chemistry / Q000378:metabolism; D007501:Iron / Q000737:chemistry* / Q000378:metabolism; D019190:Iron Overload / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008027:Light; D045726:Metalloproteases / Q000737:chemistry / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress; D055668:Photochemical Processes; D011355:Prodrugs / Q000737:chemistry* / Q000378:metabolism / Q000627:therapeutic use; D011725:Pyridines / Q000737:chemistry / Q000378:metabolism
D002614:Chelating Agents; D006912:Hydroxyquinolines; D011355:Prodrugs; D011725:Pyridines; D003300:Copper; D006861:Hydrogen Peroxide; D007501:Iron; D006867:Hydrolases; D045726:Metalloproteases
Copper; Iron; Metal chelation; Metal dyshomeostasis; Oxidative stress; Prodrug