Four Alkaloids from Alstonia scholaris with Antitumor Activity via Disturbing Glutathione Homeostasis

Alstoschoquinolines A–D (1–4) representing three unprecedented scaffolds were isolated from the leaves of Alstonia scholaris through direct separation by LC/MS detection. 1 and 2 consisted of a 5/6/5-coupled quinoline architecture containing six consecutive chiral carbons, while 3 and 4 possessed a bridged ring featuring 6/6/6/6 and 6/6/8/6 skeletons, respectively. They might be derived from the corynantheine-type indole alkaloid via sequential oxidation and rearrangement. Compound 3 exhibited a significant inhibitory effect on colon carcinoma cells by disturbing glutathione circulation.阿尔斯托喹啉类A-D（1~4）具有三种前所未有的骨架结构，研究人员借助液相色谱-质谱（LC/MS）检测指导的直接分离方法，从糖胶树（Alstonia scholaris）的叶片中分离得到该类化合物。化合物1与2拥有5/6/5稠合的喹啉母核，结构中包含六个连续的手性碳原子；而化合物3与4分别带有桥环结构，其骨架类型分别为6/6/6/6型与6/6/8/6型。该类化合物可能通过连续氧化与重排反应，由柯楠因型（corynantheine-type）吲哚生物碱衍生得到。化合物3可通过干扰谷胱甘肽循环，对结肠癌细胞表现出显著的抑制活性。