Design, synthesis, in-silico and biological evaluation of novel chalcone derivatives as multi-function agents for the treatment of Alzheimer's disease.

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ID: 125664
2019
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Abstract
A series of novel chalcone derivatives was designed, synthesized and evaluated as multifunctional agents for the treatment of AD. Among of these synthesized compounds, compound TM-2 was a selective BuChE inhibitor (IC = 2.6 μM) and selective MAO-B inhibitor (IC = 5.3 μM), which were supported by docking study. Compound TM-2 also showed good antioxidant activity, and was a selective metal chelator, as well as a neuroprotectant. Moreover, compound TM-2 could significantly inhibit self-induced and Cu-induced Aβ aggregation with 70.2% and 80.7% inhibition rate, respectively, and could disaggregate Cu-induced Aβ aggregation (73.5%), the further TEM images observed provided rational explanation. Besides, compound TM-2 displayed good PAMPA-BBB permeability and conformed to the Lipinski's rule of five. Further, compound TM-2 presented precognitive effect on scopolamine-induced memory impairment in vivo assay. Therefore, compound TM-2 might be a promising multifunctional hit compound for the treatment of AD, and the further structure optimization are in progress.
Reference Key
sang2019designeuropean Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Sang, Zhipei;Wang, Keren;Zhang, Pengfei;Shi, Jian;Liu, Wenmin;Tan, Zhenghuai;
Journal European journal of medicinal chemistry
Year 2019
DOI
S0223-5234(19)30642-7
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