Discovery of Natural IL‐8 Inhibitors From Indian Medicinal Plants, Phytochemistry and Therapeutics, Phytochemical Library for Lung Cancer Treatment Using Computational Approaches

ABSTRACT Interleukin‐8 (IL‐8) is a chemokine that regulates immune responses and inflammation but has also been implicated in cancer development and progression. In lung cancer, IL‐8 enhances tumor cell proliferation, survival, and metastasis, while also promoting angiogenesis to support tumor growth. These roles make IL‐8 a promising target for therapeutic intervention. The present study aimed to identify natural inhibitors of IL‐8 through a computational approach. A total of 17,967 phytochemicals from the IMPPAT 2.0 library were screened and refined using multiple drug‐likeness filters, including Lipinski's Rule of Five, Ghose rule, GSK 4/400, Pfizer 3/75, Veber rule, Egan rule, and QEDw = 1, yielding a focused subset of compounds. Molecular docking was then performed, resulting in the selection of two lead candidates, IMPHY004600 and IMPHY000119. Molecular dynamics simulations further evaluated their binding stability through analyses of root‐mean‐square deviation, fluctuation, gyration, solvent‐accessible surface area, hydrogen bonding, PCA, and FEL. Both compounds formed stable complexes with IL‐8, suggesting strong inhibitory potential. These findings indicate that IMPHY004600 and IMPHY000119 could serve as lead molecules for further preclinical studies, supporting the development of phytochemical‐based therapies targeting IL‐8 in lung cancer.