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ID: ALA3870350

Journal: Bioorg Med Chem Lett

Title: Synthesis and application of β-carbolines as novel multi-functional anti-Alzheimer's disease agents.

Authors: Horton W, Sood A, Peerannawar S, Kugyela N, Kulkarni A, Tulsan R, Tran CD, Soule J, LeVine H, Török B, Török M.

Abstract: The design, synthesis and assessment of β-carboline core-based compounds as potential multifunctional agents against several processes that are believed to play a significant role in Alzheimer's disease (AD) pathology, are described. The activity of the compounds was determined in Aβ self-assembly (fibril and oligomer formation) and cholinesterase (AChE, BuChE) activity inhibition, and their antioxidant properties were also assessed. To obtain insight into the mode of action of the compounds, HR-MS studies were carried out on the inhibitor-Aβ complex formation and molecular docking was performed on inhibitor-BuChE interactions. While several compounds exhibited strong activities in individual assays, compound 14 emerged as a promising multi-target lead for the further structure-activity relationship studies.

CiteXplore: 27923619

DOI: 10.1016/j.bmcl.2016.11.067