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. (C) 2016 Elsevier Inc All rights reserved.