Alkaloid Dimers Isolated from <i>Thalictrum baicalense</i> Have Antitumor Activities
Jingjing Xue, Yuetong Wang, Fangshen Liu, Hangao Yang, Bin Lin, Zhan‐Lin Li, Yongkui Jing, Dahong Li, Xu Hu
Abstract
Comprehensive Summary A pair of heterodimeric isoquinoline alkaloid enantiomers, (±) thaliberberine A, five new thalifaberine‐type aporphine‐benzylisoquinoline (ABI) alkaloids, thalicultratines M—Q, and thirteen known analogues were isolated from the roots of Thalictrum baicalense Turcz. ex Ledeb. The structures were determined by extensive spectroscopic methods and ECD calculations. Thaliberberine A featuring a novel carbon skeleton coupled by two different classes of isoquinoline alkaloids, protoberberine and phthalidoisoquinoline, represents the first natural product with the berberine skeleton substituted at C‐6. Plausible biosynthetic routes of 1 are proposed. All isolated alkaloids were screened for their antiproliferative effects in vitro against HCT116, Caco‐2, and HepG‐2 cancer cell lines. The most active ABI alkaloid, thalifaronine (7) induced G 0 /G 1 cell cycle arrest and apoptosis. Compound 7 effectively inhibited the colony formation and tumor growth of HCT116 cells in xenografts. The thalifaberine‐type ABI dimers represent a group of compounds with antitumor activity. The spectroscopic characteristics of thalifaberine‐type ABI dimers were also analyzed.