Synthesis and application of β-carbolines as novel multi-functional anti-Alzheimer's disease agents.
Synthesis and application of β-carbolines as novel multi-functional anti-Alzheimer's disease agents.
复制标题
β-碳酸盐作为新型多功能抗alzheimer疾病药物的合成和应用。
DOI：
10.1016/j.bmcl.2016.11.067
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发表时间：
2017-01-15
影响因子：
2.7
通讯作者：
Török M
中科院分区：
文献类型：
--
作者：
Horton W;Sood A;Peerannawar S;Kugyela N;Kulkarni A;Tulsan R;Tran CD;Soule J;LeVine H 3rd;Török B;Török M
设计，合成和评估的β-咔啉核心为基础的化合物作为潜在的多功能药物对几个过程，被认为是发挥重要作用的阿尔茨海默氏病（AD）的病理学，进行了描述。测定了化合物的Aβ自组装（纤维和寡聚体形成）和胆碱酯酶（AChE，BuChE）活性抑制活性，并评价了它们的抗氧化性能。为了深入了解化合物的作用模式，对乙酰胆碱-A β复合物的形成进行了HR-MS研究，并对乙酰胆碱-BuChE相互作用进行了分子对接。虽然几个化合物在单独的测定中表现出很强的活性，但化合物14成为进一步结构-活性关系研究的有希望的多靶点先导化合物。
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.