TY - JOUR
T1 - 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
AU - Gaeta, Alessandra
AU - Molina-Holgado, Francisco
AU - Kong, Xiao L
AU - Salvage, Sarah
AU - Fakih, Sarah
AU - Francis, Paul T
AU - Williams, Robert J
AU - Hider, Robert C
PY - 2011/2/1
Y1 - 2011/2/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=79551488949&partnerID=8YFLogxK
UR - http://dx.doi.org/10.1016/j.bmc.2010.12.007
U2 - 10.1016/j.bmc.2010.12.007
DO - 10.1016/j.bmc.2010.12.007
M3 - Article
SN - 1464-3391
VL - 19
SP - 1285
EP - 1297
JO - Bioorganic & Medicinal Chemistry
JF - Bioorganic & Medicinal Chemistry
IS - 3
ER -