| 葡萄糖修饰的双席夫碱的合成及其治疗阿尔茨海默病的生物活性 |
| Glucose-modified bis-Schiff bases: Synthesis and bio-activities in Alzheimer′s disease therapy |
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| 摘要: 通过微波加热方式，快速合成了3个葡萄糖修饰的双席夫碱。通过比浊度分析、HRP/Amplex Red实验、DCFH-DA荧光探针实验、NBT分析法以及MTT实验检测它们抑制金属离子诱导的Aβ聚集、减少活性氧(ROS)生成及抑制Aβ聚集产生的细胞毒性。发现葡萄糖修饰的双席夫碱都能有效抑制金属离子(Zn2+、Cu2+)诱导的Aβ1-40的聚集，降低Cu2+-Aβ加合物催化产生ROS水平、提高Cu2+-Aβ作用的细胞内超氧化物歧化酶的活力，有效抑制Zn2+或Cu2+诱导Aβ聚集而产生的神经细胞毒性并大幅提高细胞存活率。作为对比，我们也检测了相同条件下的氯碘羟喹(cliquinol,CQ)和没有葡萄糖修饰的同类双席夫碱的活性，发现葡萄糖修饰的双席夫碱各方面活性均好于CQ；葡萄糖修饰的双席夫碱自身毒性小、抗氧化和提高Aβ与金属离子共同处理的细胞的存活率方面均优于未葡萄糖官能化的同类双席夫碱。 |
| 关键词: 合成 葡萄糖 阿尔茨海默病 双席夫碱 抗氧化剂 |
| 基金项目: 重庆工商大学重点研究项目(No.2152002)资助 |
| Abstract: The dyshomeostasis of metal ions is one of the pathogeneses of Alzheimer′s disease (AD), and metal chelation therapy is a promising approach for the treatment of AD. In this work, three glucose-modified bis-Schiff bases were designed and synthesized. Their biological activities in treating AD in vitro were measured by turbidity assay, HRP/Amplex Red assay, fluorescent probe of DCFH-DA, NBT analysis, and MTT assay. The results were compared with cliquinol (CQ) and non-glucose-modified analogues. It was found that the glucose modified bis-Schiff bases had more efficient bio-activities in inhibiting metal ions (Cu2+, Zn2+) induced Aβ1-40 aggregation, decreasing the level of reactive oxygen species (ROS) in Cu2+-Aβ treated PC 12 cells, increasing the activity of superoxide dismutase in Cu2+-Aβ treated PC 12 cells and attenuating the cytotoxicity mediated by metal ions induced Aβ aggregation than CQ. The toxicity of glucose-modified bis-Schiff bases was lower than that of non-glucose functionalized analogues. The bio-activities of glucose-modified bis-Schiff bases on anti-oxidative and improving the survival rate of PC12 cells treated with Aβ and metal ions, were superior to those of non-glucose-modified analogues. |
| Keywords: synthesis glucose Alzheimer′s disease bis-Schiff base anti-oxidant |
| 投稿时间：2024-12-04 修订日期：2025-06-01 |
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