title: Biological activity of sym-triazines with acetylcholine-like substitutions as multitarget modulators of Alzheimer's disease.
abstract: The bioactivities of two novel compounds (TAE-1 and TAE-2) that contain a sym-triazine scaffold with acetylcholine-like substitutions are examined as promising candidate agents against Alzheimer's disease. Inhibition of amyloid-β fibril formation in the presence of Aβ1-42, evaluated by Thioflavin T fluorescence, demonstrated comparable or improved activity to a previously reported pentapeptide-based fibrillogenesis inhibitor, iAβ5p. Destabilization of Aβ1-42 assemblies by TAE-1 and TAE-2 was confirmed by scanning electron microscopy imaging. sym-Triazine inhibition of acetylcholinesterase (AChE) activity was observed in cytosol extracted from differentiated human SH-SY5Y neuronal cells and also using human erythrocyte AChE. The sym-triazine derivatives were well tolerated by these cells and promoted beneficial effects on human neurons, upregulating expression of synaptophysin, a synaptic marker protein, and MAP2, a neuronal differentiation marker.
authors.affiliation: Department of Physical and Environmental Sciences, University of Toronto Scarborough, 1265 Military Trail, Toronto, ON M1C 1A4, Canada.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Veloso
authors.forename: Ari M
authors.initials: AM
authors.lastname: Chow
authors.forename: Devjani
authors.initials: D
authors.lastname: Dhar
authors.forename: Derek W F
authors.initials: DW
authors.lastname: Tang
authors.forename: Hashwin V S
authors.initials: HV
authors.lastname: Ganesh
authors.forename: Svetlana
authors.initials: S
authors.lastname: Mikhaylichenko
authors.forename: Ian R
authors.initials: IR
authors.lastname: Brown
authors.forename: Kagan
authors.initials: K
authors.lastname: Kerman
mesh_terms: D000109:Acetylcholine / Q000008:administration & dosage / Q000737:chemistry*; D000544:Alzheimer Disease / Q000188:drug therapy / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000737:chemistry; D001688:Biological Products / Q000008:administration & dosage / Q000737:chemistry*; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D010446:Peptide Fragments / Q000737:chemistry; D017433:Protein Structure, Secondary; D014227:Triazines / Q000008:administration & dosage / Q000737:chemistry*
chemical_list: D016229:Amyloid beta-Peptides; D001688:Biological Products; D010446:Peptide Fragments; D014227:Triazines; C075222:amyloid beta-protein (1-42); D000109:Acetylcholine