A small bifunctional chelator that modulates Aβ42 aggregation

Multifunctional compounds that can modulate amyloid-β (Aβ) 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 1H NMR, 13C NMR, and MS. The metal-binding properties of L1 were probed by UV-visible spectroscopy to determine Cu:L stoichiometry. L1 was determined to limit Aβ 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.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author