Design, Synthesis, and Biological Evaluation of Scutellarein Carbamate Derivatives as Potential Multifunctional Agents for the Treatment of Alzheimer's Disease
Design, Synthesis, and Biological Evaluation of Scutellarein Carbamate Derivatives as Potential Multifunctional Agents for the Treatment of Alzheimer's Disease
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DOI：
10.1111/cbdd.12580
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发表时间：
2015-11
影响因子：
3
通讯作者：
Zhipei Sang;X. Qiang;Yan Li;Bei Wu;Hui Zhang;Mingsheng Zhao;Yong Deng
中科院分区：
文献类型：
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作者：
Zhipei Sang;X. Qiang;Yan Li;Bei Wu;Hui Zhang;Mingsheng Zhao;Yong Deng
基于多靶点药物设计策略，设计并合成了一系列灯盏乙素氨基甲酸酯衍生物，用于治疗阿尔茨海默病。在体外评价了它们的乙酰胆碱酯酶和丁酰胆碱酯酶抑制活性、抗氧化活性、金属螯合作用和对过氧化氢诱导的PC12细胞损伤的神经保护作用。初步结果表明，化合物7b对乙酰胆碱酯酶（AChE）和丁酰胆碱酯酶（BuChE）有较好的抑制作用，IC 50分别为1.2 ± 0.03 μm和22.1 ± 0.15 μm，并具有较强的抗氧化活性（10.3trolox当量），同时具有选择性金属螯合剂和神经保护作用。此外，7b还能改善东莨菪碱、乙醇和亚硝酸钠所致的小鼠在体被动回避记忆障碍，并能显著降低脑内乙酰胆碱酯酶的活性。本研究表明，7b可以被认为是一种潜在的抗AD多靶点药物。
A series of scutellarein carbamate derivatives were designed and synthesized based on the multitarget‐directed drug design strategy for treatment of Alzheimer's disease. Their acetylcholinesterase and butyrylcholinesterase inhibitory activities, antioxidant activities, metals chelation, and neuroprotective effects against hydrogen peroxide‐induced PC12 cell injury were evaluated in vitro. The preliminary results indicated that compound 7b exhibited good inhibitory potency toward AChE and BuChE with IC50 values of 1.2 ± 0.03 μm and 22.1 ± 0.15 μm, respectively, possessed the strong antioxidant potency (10.3 trolox equivalents), as well as acted as a selective metal chelator and neuroprotective agent. Furthermore, 7b could improve memory impairment induced by scopolamine, ethanol, and sodium nitrite using the step‐down passive avoidance task in vivo and could remarkably decrease the activity of acetylcholinesterase in mice brain. This study indicated that 7b could be considered as a potential multitarget agent against AD.