An N-Heterocyclic Amine Chelate Capable of Antioxidant Capacity and Amyloid Disaggregation

作者:Lincoln Kimberly M; Richardson Timothy E; Rutter Lauren; Gonzalez Paulina; Simpkins James W; Green Kayla N*
来源:ACS Chemical Neuroscience, 2012, 3(11): 919-927.
DOI:10.1021/cn300060v

摘要

Alzheimer%26apos;s disease is. a neurodegenerative disorder characterized by the development of intracellular neurofibrillary tangles, deposition of extracellular amyloid beta (A beta) 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 AB(1-40) 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.

  • 出版日期2012-11