Prochelator strategies for site-selective activation of metal chelators.

Valentina Oliveri, Graziella Vecchio

Journal: Journal of inorganic biochemistry 2017;162():31-43

PMID: 27297691

Full Text on Elsevier Science View on PubMed

Abstract

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.

Address: 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: [email protected].; 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.

DOI: 10.1016/j.jinorgbio.2016.05.012

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MeSH Terms: Chelating Agents, Copper, Humans, Hydrogen Peroxide, Hydrolases, Hydroxyquinolines, Iron, Iron Overload, Light, Metalloproteases, Neurodegenerative Diseases, Oxidative Stress, Photochemical Processes, Prodrugs, Pyridines