发现含硼化合物作为β淀粉样蛋白聚集抑制剂和抗氧化剂用于治疗阿尔茨海默病。
Discovery of boron-containing compounds as Aβ aggregation inhibitors and antioxidants for the treatment of Alzheimer's disease.
作者信息
Lu Chuan-Jun, Hu Jinhui, Wang Zechen, Xie Shishun, Pan Tingting, Huang Ling, Li Xingshu
机构信息
College of Chemical Engineering , Zhejiang University of Technology , Hangzhou 310014 , China.
Institute of Drug Synthesis and Pharmaceutical Process , School of Pharmaceutical Sciences , Sun Yat-sen University , Guangzhou 510006 , China . Email:
出版信息
Medchemcomm. 2018 Sep 12;9(11):1862-1870. doi: 10.1039/c8md00315g. eCollection 2018 Nov 1.
Abstract
A novel series of boron-containing compounds were designed, synthesized and evaluated as multi-target-directed ligands against Alzheimer's disease. The biological activity results demonstrated that these compounds possessed a significant ability to inhibit self-induced Aβ aggregation (20.5-82.8%, 20 μM) and to act as potential antioxidants (oxygen radical absorbance capacity assay using fluorescein (ORAC-FL) values of 2.70-5.87). In particular, compound is a potential lead compound for AD therapy (IC = 3.41 μM for self-induced Aβ aggregation; ORAC-FL value = 4.55). Compound also functions as a metal chelator. These results indicated that boron-containing compounds could be new structural scaffolds for the treatment of AD.
摘要
设计、合成了一系列新型含硼化合物，并将其作为针对阿尔茨海默病的多靶点导向配体进行了评估。生物活性结果表明，这些化合物具有显著抑制自身诱导的Aβ聚集的能力（20 μM时为20.5 - 82.8%），并可作为潜在的抗氧化剂（使用荧光素的氧自由基吸收能力测定（ORAC-FL）值为2.70 - 5.87）。特别地，化合物 是AD治疗的潜在先导化合物（自身诱导的Aβ聚集的IC = 3.41 μM；ORAC-FL值 = 4.55）。化合物 还可作为金属螯合剂。这些结果表明，含硼化合物可能是治疗AD的新型结构骨架。
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