A small bifunctional chelator that modulates A beta(42) aggregation

作者：Zhang, Chaofeng^*; Gomes, Luiza M. F.; Zhang, Tonglu; Storr, Tim^*

来源：Canadian Journal of Chemistry, 2018, 96(1): 78-82.

DOI：10.1139/cjc-2017-0623

• beta-amyloid
• Alzheimer's disease
• click chemistry
• copper ions

Multifunctional compounds that can modulate amyloid-beta (A beta) aggregation and interact with metal ions hold considerable promise as therapeutic agents for Alzheimer's disease (AD). Using the copper-catalyzed azide-alkyne cycloaddition reaction, a novel bifunctional chelator 2-(1-(4-(dimethylamino) benzyl)-1H-1,2,3-triazol-4-yl) phenol (L1) was synthesized. L1 contains a bidentate metal-binding unit and a pendant dimethylamino moiety. The product was characterized by H-1 NMR, C-13 NMR, and MS. The metal-binding properties of L1 were probed by UV-vis spectroscopy to determine Cu: L stoichiometry. L1 was determined to limit A beta aggregation at 48 h via a ThT assay. In addition, L1 complies with Lipinski's rules and calculated logBB values for potential drug likeness and BBB permeability. These results suggest that L1 is a suitable candidate for further study as a multifunctional compound to treat AD.

• 出版日期2018-1
• 单位太原理工大学