State Key Laboratory of Bioactive Molecules and Druggability Assessment, Jinan University, Guangzhou, 510632, China; Center for Bioactive Natural Molecules and Innovative Drugs Research, Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou, 510632, China.
Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, the NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences and the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, 511436, China.
Phytochemistry. 2024 Dec;228:114245. doi: 10.1016/j.phytochem.2024.114245. Epub 2024 Aug 10.
Kopsileuconines A-D (1-4), four monoterpenoid bisindole alkaloids with unprecedented skeletons, along with their biosynthetically related precursors (5-8) were isolated from the roots of Kopsia hainanensis. Compound 1 possessed an undescribed C-6-C-5' dimerization pattern of aspidofractinine-type alkaloids. Compounds 2-4 were rhazinilam-kopsine (2) and rhazinilam-aspidofractinine type (3 and 4) bisindole alkaloids with undescribed skeletons, respectively. Their structures with absolute configurations were fully accomplished by extensive spectroscopic analysis, quantum-chemical calculations, and X-ray crystallography. A plausible biosynthetic pathway for 1-4 was proposed. Compound 2 exhibited a significant inhibitory effect against human lung cancer cell lines PC9 (EGFR mutant), with an IC value of 15.07 ± 1.19 μM.
从海南钩吻的根部分离得到了钩吻素内酯 A-D（1-4），这四个具有前所未有的骨架的单萜双吲哚生物碱，以及它们生物合成相关的前体（5-8）。化合物 1 具有未知的 aspidofractinine 型生物碱的 C-6-C-5' 二聚化模式。化合物 2-4 分别为 rhazinilam-kopsine（2）和 rhazinilam-aspidofractinine 型（3 和 4）双吲哚生物碱，具有未知的骨架。通过广泛的光谱分析、量子化学计算和 X 射线晶体学，确定了它们的结构和绝对构型。提出了一个可能的生物合成途径。化合物 2 对人肺癌细胞系 PC9（EGFR 突变）表现出显著的抑制作用，IC 值为 15.07±1.19μM。
