Add time:09/27/2019         Source:sciencedirect.com

A new series of tacrine-coumarin hybrids linked to 1,2,3-triazole were designed, synthesized, and tested as potent dual binding site cholinesterase inhibitors (ChEIs) for the treatment of Alzheimer’s disease (AD). Among them, compound 8e was the most potent anti-AChE derivative (IC50 = 27 nM) and compound 8m displayed the best anti-BChE activity (IC50 = 6 nM) much more active than tacrine and donepezil as the reference drugs. Compound 8e was also evaluated for its BACE1 inhibitory activity and neuroprotectivity against PC12 cells exposed to Aβ25-35 which indicated low activity. Finally, in vivo studies by Morris water maze task showed that compound 8e significantly reversed scopolamine-induced memory deficit in rats.

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