An N-Heterocyclic Amine Chelate Capable of Antioxidant Capacity and Amyloid Disaggregation
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- 作者：Kimberly M. Lincoln ; Timothy E. Richardson ; Lauren Rutter ; Paulina Gonzalez ; James W. Simpkins ; Kayla N. Green
- 刊名：ACS Chemical Neuroscience
- 出版年：2012
- 出版时间：November 21, 2012
- 年：2012
- 卷：3
- 期：11
- 页码：919-927
- 全文大小：394K
- 年卷期：v.3,no.11(November 21, 2012)
- ISSN：1948-7193
文摘
Alzheimer鈥檚 disease is a neurodegenerative disorder characterized by the development of intracellular neurofibrillary tangles, deposition of extracellular amyloid beta (A尾) plaques, along with a disruption of transition metal ion homeostasis in conjunction with oxidative stress. Spectroscopic, transmission electron microscopy, and scanning electron microscopy imaging studies show that 1 (pyclen) is capable of both preventing and disrupting Cu2+ induced AB1鈥?0 aggregation. The pyridine backbone of 1 engenders antioxidant capacity, as shown by cellular DCFH-DA (dichlorodihydrofluorescein diacetate) assay in comparison to other N-heterocyclic amines lacking this aromatic feature. Finally, 1 prevents cell death induced by oxidative stress as shown by the Calcein AM assay. The results are supported using density functional theory studies which show that the pyridine backbone is responsible for the antioxidant capacity observed.