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| 青藤碱N-取代衍生物的合成及抑制NF-κB转录活性作用 |
| 杨帆1,2,管忠俊2,柴晓云2,吴秋业1,2,孟庆国1* |
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(1. 烟台大学药学院药物化学教研室, 烟台 264005;
2. 第二军医大学药学院有机化学教研室, 上海 200433
*通信作者) |
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| 摘要: |
| 目的 设计合成一类青藤碱衍生物,并研究其体外抗炎活性。方法 以青藤碱为原料,经脱N-甲基、亲核取代、经典的Click Reaction,共合成9个青藤碱衍生物,考察所得化合物体外对NF-κB转染的影响。结果 合成的目标化合物均为首次报道,并经1HNMR和LC-MS确证结构。所得化合物体外对NF-κB转染均具有一定的抑制作用,但活性较青藤碱有所下降。结论 N原子上引入较大基团或者长链可能会降低青藤碱的抗炎活性。 |
| 关键词: 青藤碱 修饰 NF-κB 消炎药 |
| DOI：10.3724/SP.J.1008.2015.00413 |
| 投稿时间：2014-10-11修订日期：2014-11-24 |
| 基金项目:上海市科委重点攻关项目(08431903003). |
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| Synthesis of N-substituted sinomenine derivatives and its inhibitory effect against NF-κB transcriptional activity |
| YANG Fan1,2,GUAN Zhong-jun2,CHAI Xiao-yun2,WU Qiu-ye1,2,MENG Qing-guo1* |
(1. Department of Medicinal Chemistry, School of Pharmacy, Yantai University, Yantai 264005, Shandong, China;
2. Department of Organic Chemistry, College of Pharmacy, Second Military Medical University, Shanghai 200433, China
*Corresponding author) |
| Abstract: |
| Objective To design and synthesize a series of sinomenine derivatives and to investigate their anti-inflammation activities in vitro. Methods Nine sinomenine derivatives were synthesized via demethylate of N atom, nucleophilic substitution and classical Click Reaction using sinomenine as the starting material. The target compounds were evaluated for their influence on NF-κB transcriptional activity in vitro. Results All the synthesized compounds were reported for the first time, and they were confirmed by 1HNMR and LC-MS. Biological studies showed that all the synthetic derivatives exhibited certain inhibitory effect against NF-κB transfection in vitro, but was weaker than that of sinomenine. Conclusion Replacing N-methyl with large group or long side chain on nitrogen atom may weaken the anti-inflammatory activity of sinomenine. |
| Key words: sinomenine modification NF-κB anti-inflammatory agents |
