Division of Pharmaceutical Science, King's College, Franklin-Wilkins Building, Waterloo Campus, Stamford Street, London SE1 9NH, UK.
Bioorg Med Chem. 2011 Feb 1;19(3):1285-97. doi: 10.1016/j.bmc.2010.12.007. Epub 2010 Dec 13.
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.
本文描述了一类新型的 2-酰胺基-3-羟基吡啶-4-酮铁螯合剂。这些化合物被设计为合适的分子探针，以提高我们对铁在神经退行性疾病中的作用的认识。神经退行性疾病，如阿尔茨海默病（AD）和帕金森病（PD），可以被视为具有不同病理表现的疾病，它们共享关键的代谢过程，如蛋白质聚集和氧化应激。有趣的是，这两种代谢改变似乎都与金属离子（包括铁）的参与有关。因此，铁螯合作用是一种有潜力的治疗方法。为了获得治疗神经退行性疾病的合适方案，对这些螯合剂的物理化学性质（pK(a)、pFe(3+) 和 logP）和生物学性质（对含铁酶的抑制作用）进行了研究。神经元细胞培养研究证实，新型铁螯合剂对β-淀粉样蛋白诱导的毒性具有神经保护作用。
