title: An N-heterocyclic amine chelate capable of antioxidant capacity and amyloid disaggregation.
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.
authors.affiliation: Department of Chemistry, Texas Christian University, 2800 S. University, Ft. Worth, Texas 76129, United States.
authors.forename: Kimberly M
authors.initials: KM
authors.lastname: Lincoln
authors.forename: Timothy E
authors.initials: TE
authors.lastname: Richardson
authors.forename: Lauren
authors.initials: L
authors.lastname: Rutter
authors.forename: Paulina
authors.initials: P
authors.lastname: Gonzalez
authors.forename: James W
authors.initials: JW
authors.lastname: Simpkins
authors.forename: Kayla N
authors.initials: KN
authors.lastname: Green
mesh_terms: D000588:Amines / Q000494:pharmacology*; D016229:Amyloid beta-Peptides / Q000187:drug effects*; D000975:Antioxidants / Q000494:pharmacology; D053961:Azabicyclo Compounds / Q000494:pharmacology; D002614:Chelating Agents / Q000494:pharmacology*; D003300:Copper / Q000494:pharmacology; D006571:Heterocyclic Compounds / Q000494:pharmacology*; D006801:Humans; D008024:Ligands; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D009391:Nephelometry and Turbidimetry; D018384:Oxidative Stress / Q000187:drug effects; D014131:Trace Elements / Q000494:pharmacology; D014443:Tyrosine; D015032:Zinc / Q000494:pharmacology
chemical_list: D000588:Amines; D016229:Amyloid beta-Peptides; D000975:Antioxidants; D053961:Azabicyclo Compounds; D002614:Chelating Agents; D006571:Heterocyclic Compounds; D008024:Ligands; D014131:Trace Elements; C582723:pyclen; D014443:Tyrosine; D003300:Copper; D015032:Zinc