Structurally diverse triterpenoid alkaloids from Buxus myrica with cytotoxic and apoptosis-inducing activities

Sixteen triterpenoid alkaloids, including twelve previously undescribed ones named myribuxines A–L ( 1 – 12 ), were isolated from the twigs and leaves of Buxus myrica H. Lév. To our knowledge, this species has not yet undergone any phytochemical or pharmacological investigation. Their structures and relative configurations were elucidated by comprehensive spectroscopic analysis and DP4 + probability calculations, with their absolute configurations tentatively assigned on the basis of the biosynthetic origin of Buxus alkaloids. Structurally, 5 , 6 , 7 , and 12 feature a rare C-16 aromatic ester substituent, while 9 , 10 , and 11 possess a rare tetrahydrofuran ring formed by a C-10–O–C-23 ether linkage. All isolated alkaloids were evaluated for cytotoxicity against HepG2, A549, U251, and HCT-116 cell lines. The active alkaloids showed modest cytotoxicity, with half maximal inhibitory concentration (IC 50 ) values ranging from 17.5 to 47.3 μM across the four cell lines. Among them, 2 exhibited modest inhibitory activity toward HepG2 cells. Flow cytometry analysis revealed that 2 promoted apoptosis in a dose- and time-dependent manner. Furthermore, network pharmacology screening predicted HSP90α as its potential molecular target. Follow-up molecular docking further revealed the binding model between compound 2 and HSP90.