Artemdubins A–E from Artemisia dubia var. subdigitata: antihepatoma activity, molecular docking and molecular dynamics studies

Abstract

Artemdubins A–E (1, 3, 4, 8, 16), five undescribed sesquiterpenoids, along with 18 known ones were isolated from Artemisia dubia var. subdigitata (Asteraceae). Their structures and absolute configurations were determined via spectroscopic data, equivalent circulating density (ECD) and nuclear magnetic resonance (NMR) calculations with DP4+ analyses. Chemically, artemdubins A–E were classified as guaiane-type sequiterpenoid dimer, endesmanolide, and cadinane. Antihepatoma assay suggested that compound 12 exhibited inhibitory activity on HepG2, Huh7 and SK-Hep-1 cells with IC₅₀ values of 14.1, 12.9, and 7.1 μM, respectively, which were equivalent to those of sorafenib. Network pharmacological analysis and molecular docking revealed that estrogen receptor 1 (ESR1) might be a potential target of compound 12 with high binding affinity (total score: 4.6). Moreover, molecular dynamics simulation studies provided further insight into the stable and potent interaction mechanism.