Benzylisoquinoline alkaloid dimers with antitumor activities from Thalictrum wangii B. Boivin

Eight previously undescribed benzylisoquinoline alkaloid dimers, neothalfines A-H (1-8), alongside thirteen known analogs (9-21), were isolated from roots of Thalictrum wangii B. Boivin. The structures and absolute configurations were elucidated based on extensive spectroscopic data (HRESIMS, NMR, and IR) in conjunction with TDDFT-ECD calculations. Evaluation of all identified alkaloids revealed that twelve dimers inhibited marked anti-proliferative activity against three human cancer cell lines (A549, MHCC97H, and U-87MG) with IC₅₀ values ranging from 2.1 to 38.1 μM. Among them, dimer 8 was particularly potent, displaying IC₅₀ values of 3.5, 2.1, and 2.8 μM against the respective cell lines, outperforming the positive control. Mechanistic studies revealed that 8 induces mitochondrial dysfunction, ROS-mediated apoptosis, and inhibits colony formation. Network pharmacology and molecular docking identified SRC, EGFR, and GSK3β as core targets, further supporting its role in mitochondrial energy metabolism dysregulation.