2025
Pecanthines A–C, unprecedented dimericβ-carboline alkaloids from the seeds ofPeganum harmala.
Publication Information
Title:Pecanthines A–C, unprecedented dimericβ-carboline alkaloids from the seeds ofPeganum harmala.
Author(s):Qing Tang#,Kai Zhao#, Hui-Hui Zhu#, Qiang Lin, Hai-Yue Zhao, Wei-Xuan Zheng, Zhong-Nan Wu, Hao Wang*, Guo-Cai Wang*,Yu-Bo Zhang*.
Journal Name, Year, Volume(Issue): Page range:
Chinese Chemical Letters, 2025, in press.
DOI:https://doi.org/10.1016/j.cclet.2025.112172
Abstract:Three novel β-carboline alkaloid dimers, pecanthines A–C (1−3), featuring unprecedented 6/5/6/6-5/6 and 6/5/6/6/5/6 polycyclic frameworks, were isolated from the seeds of Peganum harmala. Their structures were elucidated by spectroscopic analyses and X-ray diffraction. Notably, compounds 1 and 2 represent the first heterodimeric alkaloids merging canthin-6-one and melatonin-type scaffolds, with 1 additionally displaying neuroprotective activity. In addition, a gram-scale synthesis of 3 was achieved in six steps, leveraging a key acyl-ketene imine condensation and Suzuki coupling. Biological evaluation revealed that 3 acts as a new topoisomerase I (Topo I) inhibitor, exhibiting remarkable antiproliferative activity. Mechanistic studies demonstrated that 3 induces DNA damage, triggering apoptosis and cell cycle arrest in cancer cells. The discovery and gram-scale synthesis of 3 provide a promising lead compound and a novel molecular scaffold for anticancer drug development.
