Kopsileuconines A−D: Bisindole alkaloids with cytotoxic activity from Kopsia hainanensis

• Published in: Phytochemistry (Oxford) 2024-12, Vol.228, p.114245, Article 114245
• Main Authors: Li, Ni-Ping, Chen, Shan-Na, Su, Wei-Fang, Liu, Fen, Li, Lian-Jing, Song, Jian-Guo, Cheng, Min-Jing, Li, Yi-Yi, Chen, Run-Qiang, Lei, Xue-Ping, Ye, Wen-Cai, Wang, Lei
• Format: Article
• Language: English
• Subjects: Apocynaceae; Cytotoxic activity; Kopsia hainanensis; Monoterpenoid bisindole alkaloids; Structure elucidation
• ISSN: 0031-9422; 1873-3700; 1873-3700
• DOI: 10.1016/j.phytochem.2024.114245

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 IC50 value of 15.07 ± 1.19 μM. Four monoterpenoid bisindole alkaloids (1−4) with unprecedented skeletons, along with their biosynthetically related precursors (5−8) were isolated from the roots of Kopsia hainanensis. Compound 2 displayed a significant inhibitory effect against human lung cancer cell lines PC9 (EGFR mutant). [Display omitted] •Four monoterpenoid bisindole alkaloids with unprecedented skeletons were isolated from the roots of Kopsia hainanensis.•Compounds 2−4 were rhazinilam-kopsine (2) and rhazinilam-aspidofractinine type (3 and 4) bisindole alkaloids , respectively.•Compound 2 significantly induced the apoptosis of PC9 cells.