Synthesis, physical-chemical characterisation and biological evaluation of novel 2-amido-3-hydroxypyridin-4(1H)-ones: Iron chelators with the potential for treating Alzheimer's disease

Abstract

A novel class of 2-amido-3-hydroxypyridin-4-one iron chelators is described. These compounds have been designed to behave as suitable molecular probes which will improve our knowledge of the role of iron in neurodegenerative conditions. Neurodegenerative disorders, such as Alzheimer's disease (AD) and Parkinson disease (PD), can be considered as diverse pathological conditions sharing critical metabolic processes such as protein aggregation and oxidative stress. Interestingly, both these metabolic alterations seem to be associated with the involvement of metal ions, including iron. Iron chelation is therefore a potential therapeutic approach. The physico-chemical (pK(a), pFe(3+) and logP) and biological properties (inhibition of iron-containing enzymes) of these chelators have been investigated in order to obtain a suitable profile for the treatment of neurodegenerative conditions. Studies with neuronal cell cultures confirm that the new iron chelators are neuroprotective against β-amyloid-induced toxicity.