Bioassay-guided isolation of hepatoprotective lignans from Vernonia cinerea: DeepSAT-driven structural elucidation and predictive mechanistic insights against drug-induced liver injury†

Three new dibenzylbutane lignans, vernolignans A–C (1–3), along with three known compounds (4–6), were isolated from Vernonia cinerea through a bioactivity-guided isolation process. The planar structures of the new compounds (1–3) were elucidated through comprehensive analysis of HR-ESI-MS and 1D/2D NMR data, with the assistance of AI-based structure annotation tool DeepSAT. The absolute configurations of 1–3 were determined by comparing the experimental and calculated ECD spectra. Compounds 2 and 3 exhibited significant improvements in cell viability and attenuated acetaminophen-induced alanine aminotransferase levels in murine hepatocytes at 20 μM. Bioinformatics analysis and molecular docking suggested that BRAF might be a potential target for these lignans.