Synthesis and application of β-carbolines as novel multi-functional anti-Alzheimer’s disease agents

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• 作者：William Horton^a ; Abha Sood^a ; Swarada Peerannawar^a ; Nandor Kugyela^a ; Aditya Kulkarni^a ; Rekha Tulsan^a ; Chris D. Tran^a ; Jessica Soule^a ; Harry LeVine III^b ; Bé ; la Tö ; rö ; k^a ; Marianna Tö ; rö ; k^a ; ^{marianna.torok@umb.edu}
• 关键词：Alzheimer&rsquo ; s disease ; Amyloid beta ; Cholinesterase inhibition ; Antioxidant ; β-Carbolines
• 刊名：Bioorganic & Medicinal Chemistry Letters
• 出版年：2017
• 出版时间：15 January 2017
• 年：2017
• 卷：27
• 期：2
• 页码：232-236
• 全文大小：1184 K
• 卷排序：27

文摘

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.