Chen Chen, Liu Jian-Wen, Guo Ling-Li, Xiong Feng, Ran Xiao-Qian, Guo Ya-Rong, Yao Yong-Gang, Hao Xiao-Jiang, Luo Rong-Can, Zhang Yu
State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, Yunnan, China.
Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, And KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650204, Yunnan, China; Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, 650201, Yunnan, China.
Phytochemistry. 2022 Nov;203:113392. doi: 10.1016/j.phytochem.2022.113392. Epub 2022 Aug 27.
Three undescribed monoterpenoid indole alkaloid dimers (kopoffines A-C, which are connected via a methylene unit) and with nine known alkaloids were isolated and identified from the fruits of Kopsia arborea Blume. Their structures, including their absolute configurations, were established by HRESIMS, NMR, single-crystal X-ray diffraction, and ECD analyses. Kopoffines A-C showed significant inhibition against cyclin-dependent kinase 5 (IC: 0.34-2.18 μM). Western blotting analyses showed that kopoffines A-C significantly decreased the protein levels of CDK5 and phospho-CDK5 (Tyr15) (pCDK5) at concentrations of 2.5 and 10 μM. The levels of phospho-Tau (Thr217) (pTau217, a new biomarker of AD), and phospho-Tau (Ser396) (pTau396), which play major roles in the formation of neurofibrillary tangles , were decreased by the kopoffines A-C treatment. Molecular docking studies indicated that kopoffines A-C could form stable interactions with CDK5.
从乔木鸡骨常山（Kopsia arborea Blume）的果实中分离并鉴定出三种未描述的单萜吲哚生物碱二聚体（kopoffines A - C，通过亚甲基单元连接）以及九种已知生物碱。它们的结构，包括其绝对构型，通过高分辨电喷雾电离质谱（HRESIMS）、核磁共振（NMR）、单晶X射线衍射和电子圆二色光谱（ECD）分析得以确定。Kopoffines A - C对细胞周期蛋白依赖性激酶5显示出显著抑制作用（IC：0.34 - 2.18 μM）。蛋白质免疫印迹分析表明，在浓度为2.5和10 μM时，kopoffines A - C显著降低了CDK5和磷酸化CDK5（Tyr15）（pCDK5）的蛋白质水平。在神经原纤维缠结形成中起主要作用的磷酸化 Tau（Thr217）（pTau217，一种新的阿尔茨海默病生物标志物）和磷酸化 Tau（Ser396）（pTau396）的水平，经kopoffines A - C处理后降低。分子对接研究表明，kopoffines A - C可与CDK5形成稳定的相互作用。
