2-去氢表雄酮苯亚甲基衍生物的合成及抗炎活性研究
收稿日期: 2019-01-25
修回日期: 2019-03-22
网络出版日期: 2019-04-11
基金资助
国家自然科学基金（Nos.21402178，U1603125）和河南省科学研究基金（No.132300410195）资助项目.
Synthesis and Anti-inflammatory Activity Evaluation of 2-Dehydroepiandrosterone Benzene Methyl Derivatives
Received date: 2019-01-25
Revised date: 2019-03-22
Online published: 2019-04-11
Supported by
Project supported by the National Natural Science Foundation of China (Nos. 21402178, U1603125) and the Scientific Research Fund of Henan Province (No. 132300410195).
阿尔茨海默症作为21世纪全球主要健康危机之一，由于其发病机制的复杂性，目前还未找到很好的解决办法.为了找到更加经济有效的治疗神经退行性疾病的药物，合成了一系列新型2-去氢表雄酮苯亚甲基衍生物，并研究了其对脂多糖（LPS）激活小胶质细胞株BV-2 NO释放及细胞存活率的影响.结果表明所合成化合物作用24 h后，对LPS活化的小鼠小胶质细胞株BV2的NO释放均有不同程度的抑制作用，且具有一定的浓度依赖性.活性最好的化合物15β，16β-亚甲基雄甾-2-（3-氯）-苯亚甲基-4，6-二烯-3，17-二酮（5a）和15β，16β-亚甲基雄甾-2-（3，4，5-三甲氧基）-苯亚甲基-4，6-二烯-3，17-二酮（5j）的IC50值分别为2.69和3.28 μmol·L-1，优于阳性对照米诺环素.此类化合物在涉及活化小胶质细胞的神经退行性疾病方面的作用值得进一步研究.
朱丽 , 杨艳秋 , 高佩佩 , 安雪 , 孙莹莹 , 孙晓雯 , 侯悦 , 单丽红 . 2-去氢表雄酮苯亚甲基衍生物的合成及抗炎活性研究[J]. 有机化学, 2019 , 39(9) : 2625 -2631 . DOI: 10.6023/cjoc201901039
Alzheimer's Disease (AD) is one of the major health crises in the 21st century, and due to the complexity of its pathogenesis, there has no good solution to cure this disease. In order to find more economical and effective drugs for the treatment of neurodegenerative diseases, a series of novel 2-dehydroepiandrosterone benzathine derivatives were synthesized and their activity on the NO release of microglia cell line BV-2 activated by lipopolysaccharide (LPS), as well as their effect on cell viability were studied. The structures of the synthesized compounds were confirmed by 1H NMR, 13C NMR and HRMS. The results showed that all compounds had inhibitory effects on the NO release of LPS-activated mouse microglial cell line BV2 after 24 h of treatment, and it was dose-dependent. In particular, the IC50 values of 2-(3-chloro)benzylidene-15β,16β-methylene-androstane-4,6-diene-3,17-dione (5a) and 2-(3,4,5-trimethoxy)benzylidene-15β,16β-methylene-androstane-4,6-die-ne-3,17-dione (5j) were 2.69 and 3.28 μmol·L-1, respectively, which were better than the positive control Minocycline. The results showed that these compounds may be effective in the development of neurodegenerative diseases involving activation of microglia, and the mechanism deserved further study.
Key words： dehydroepiandrosterone; chalcone analogue; alzheimer's disease; microglia
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