An N-heterocyclic amine chelate capable of antioxidant capacity and amyloid disaggregation

ACS Chem Neurosci. 2012 Nov 21;3(11):919-27. doi: 10.1021/cn300060v. Epub 2012 Aug 31.

Abstract

Alzheimer's disease is a neurodegenerative disorder characterized by the development of intracellular neurofibrillary tangles, deposition of extracellular amyloid beta (Aβ) 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 Cu(2+) 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amines / pharmacology*
  • Amyloid beta-Peptides / drug effects*
  • Antioxidants / pharmacology
  • Azabicyclo Compounds / pharmacology
  • Chelating Agents / pharmacology*
  • Copper / pharmacology
  • Heterocyclic Compounds / pharmacology*
  • Humans
  • Ligands
  • Microscopy, Electron, Scanning
  • Microscopy, Electron, Transmission
  • Nephelometry and Turbidimetry
  • Oxidative Stress / drug effects
  • Trace Elements / pharmacology
  • Tyrosine
  • Zinc / pharmacology

Substances

  • Amines
  • Amyloid beta-Peptides
  • Antioxidants
  • Azabicyclo Compounds
  • Chelating Agents
  • Heterocyclic Compounds
  • Ligands
  • Trace Elements
  • pyclen
  • Tyrosine
  • Copper
  • Zinc