Biological Activity of sym-Triazines with Acetylcholine-like Substitutions as Multitarget Modulators of Alzheimer’s Disease

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...

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Veröffentlicht in:ACS chemical neuroscience 2013-06, Vol.4 (6), p.924-929
Hauptverfasser: Veloso, Anthony J, Chow, Ari M, Dhar, Devjani, Tang, Derek W. F, Ganesh, Hashwin V.S, Mikhaylichenko, Svetlana, Brown, Ian R, Kerman, Kagan
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Sprache:eng
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Zusammenfassung: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.
ISSN:1948-7193
1948-7193
DOI:10.1021/cn400028w