In Vitro Cytotoxic Activity and Predictive Computational Characterization of Aromadendrene Oxide‐2 in Human Cancer Cell Lines Using Molecular Docking, Residue Interaction Network, and DFT Analyses

ABSTRACT Aromadendrene oxide‐2 (AO‐2), a sesquiterpene derivative, was evaluated for its cytotoxic potential against five human tumor cell lines (HT‐29, MiaPaCa‐2, HL‐60, A549, and MDA‐MB‐231). AO‐2 exhibited dose‐dependent antiproliferative effects, with the highest sensitivity observed in HT‐29, MiaPaCa‐2, and HL‐60 cells, while A549 and MDA‐MB‐231 cells displayed a more resistant profile. ADMET analyses indicated that AO‐2 possesses favorable pharmacokinetic properties, including high gastrointestinal absorption, blood–brain barrier permeability, and moderate oral bioavailability, although notable differences were observed in metabolic interactions and transporter properties compared to the reference ligand CID 66713599. Molecular docking studies revealed that AO‐2 interacts with the Bcl‐2 protein with a binding energy of −7.2 kcal/mol, demonstrating reasonable ligand efficiency and suitable binding quality. Density functional theory (DFT) analysis showed a HOMO–LUMO energy gap of 0.31741 eV, reflecting moderate electronic reactivity, high molecular softness, and weak electrophilic character. Collectively, these findings support that AO‐2 is a bioactive sesquiterpene with moderate cytotoxicity and promising pharmacokinetic and molecular interaction profiles, providing a computational and experimental basis for further mechanistic investigations in anticancer research.