Phytochemical Profiling and Multitargeted Anticancer Potential of Achillea alimeana: An In Vitro and In Silico Evaluation of Lung Cancer Cells

Achillea alimeana , a newly identified plant, was investigated for its antioxidant, anticancer, and anti‐inflammatory properties. HPLC analysis revealed ten major phytochemicals, predominantly chlorogenic acid (624.9 µg/g) and rutin (455.7 µg/g). The water extract showed strong antioxidant activity and selective cytotoxicity against the lung cancer cell lines A549 and H1975. Apoptotic and nonapoptotic cell death was validated by Annexin‐V/PI staining, luciferase assays, and RT‒PCR, alongside reduction in cell migration and invasion. Anti‐inflammatory effects are linked to iNOS and NF‐κB response elements downregulation. Molecular docking studies were performed for the ten phytochemicals against VEGFR2, MDM2, BCL‐2, and iNOS targets. Chlorogenic acid emerged as the most promising molecule, exhibiting the best IFD Glide XP docking scores (−12.061 kcal/mol for VEGFR2, −10.490 for MDM2, −11.610 for BCL‐2, and −9.276 for iNOS) and favorable MM‐GBSA Δ G binding energies (−72.79, −50.20, −66.02, and −67.41 kcal/mol, respectively). Furthermore, 250 ns molecular dynamics simulations confirmed the stable interactions of chlorogenic acid with VEGFR2 and MDM2. The chlorogenic acid‐VEGFR2 complex showed high stability, with protein and ligand RMSD values of 1.75 and 1.25 Å, respectively. These findings highlight A. alimeana as a promising source of bioactive compounds for lung cancer therapy.