Synthesis, anti-tumor activity, biological evaluation, network pharmacology and molecular dynamics simulation of Dehydroabietylamine chromone derivatives

The Vilsmeier reagent was prepared from N, N-dimethylformamide and POCl₃. Cyclization with 2-hydroxyacetophenone derivatives followed by Pinnick oxidation afforded 3-carboxychromone intermediates. Subsequent condensation with dehydroabietylamine yielded eight target dehydroabietylamine-chromone derivatives 1-8 . In vitro antitumor assays demonstrated that compound 3 exhibited potent inhibitory activity against HeLa, B16F10, and HepG2 cell lines with IC₅₀ values of 2.07 ± 0.18, 4.46 ± 0.23, and 3.04 ± 0.12 μM, respectively. DAPI staining and fluorescence microscopy confirmed that compound 3 induces early apoptosis and causes cell cycle arrest at the G2/M phase. Molecular electrostatic potential (MEP) and frontier molecular orbital (FMO) analyses revealed electronic distributions and reactive sites, while docking studies indicated strong binding affinities of compound 3 toward AKT1 and SRC proteins (-9.20 and -7.76 kcal/mol). Network pharmacology and molecular dynamics simulations further validated the stability of protein complexes, profiling to evaluate pharmacokinetic properties. These findings establish a foundation for developing dehydroabietylamine-chromone hybrids as promising antitumor agents.