| 李萌,林爽,曹雅婷,等.海洋来源普那布林的衍生物结构改造及其抗炎活性研究[J].中国海洋药物,2026,(4):-. |
| 海洋来源普那布林的衍生物结构改造及其抗炎活性研究 |
| Structural modification of derivatives of the marine-derived Plinabulin and their anti-inflammatory activities |
| 投稿时间：2025-04-03 修订日期：2025-05-12 |
| DOI： |
| 中文关键词: 普那布林 抗炎药物 二酮哌嗪 |
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| 中文摘要: |
| 目的 针对海洋来源的普那布林进行衍生物的设计合成并评价其抗炎活性。方法 以二酮哌嗪为骨架，经过卤素取代、酰胺缩合、Aldol缩合等反应合成普那布林衍生物，并对其进行抗炎活性评价。结果 总计合成了14个衍生物，通过初步抗炎机制研究表明，普那布林衍生物在高浓度下对NO的释放都有显著的抑制效果，其中化合物12h对RAW264.7细胞的抑制率高达95%，对正常巨噬细胞无毒性；以剂量依赖性抑制NO的释放；诱导促炎基因IL-6、IL-1β、TNF-α的表达降低，而对抗炎基因无明显作用；抑制STAT3和NFκB蛋白的磷酸化。结论 普那布林类衍生物具备用于抗炎药物开发的潜力。 |
| English Summary: |
| Objective To design, synthesize derivatives of marine-derived Plinabulin and evaluate their anti-inflammatory activity. Methods Plinabulin derivatives were synthesised by halogen substitution, amide condensation and Aldol condensation using diketopiperazine as backbone. The anti-inflammatory activities of Plinabulin derivatives were tested. Results 14 derivatives were synthesized. As initial mechanistic studies for anti-inflammatory activity, Plinabulin derivatives exhibited significant inhibitory effects on NO release at high concentrations, with compound 12h demonstrating an inhibition rate of up to 95% in RAW264.7 cells while being non-toxic to normal macrophages. It inhibits NO release in a dose-dependent manner and reduces the expression of pro-inflammatory genes such as IL-6, IL-1β, and TNF-α in a dose-dependent fashion, without significantly affecting anti-inflammatory genes. Additionally, it inhibits the phosphorylation of STAT3 and NFκB proteins. Conclusion Plinabulin derivatives show potential for development as anti-inflammatory drugs. |
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