Phytochemicals as potential inhibitors of interleukin-8 for anticancer therapy: in silico evaluation and molecular dynamics analysis

Within the realm of soluble factors that have emerged as potential targets for therapeutic intervention, the chemokine interleukin-8 (IL-8) has garnered attention as a potential contributor to treatment responses in various cancer types. The utilization of naturally occurring anticancer compounds for treating cancer patients has shown substantial advancements in survival rates across early and advanced stages of the disease. In silico research findings provide support for the application of phytochemicals as potential inhibitors of IL-8, and phytochemicals exhibiting a high binding free energy and crucial interactions display promising anticancer properties, positioning them as candidates for future drug development. Noteworthy phytochemicals such as IMPHY006634 (Isohydnocarpin), IMPHY007957 (Chitranone) and IMPHY013015 (1-Hydroxyrutaecarpine) were predicted to possess inhibitory activity against IL-8, with calculated energies ranging from -9.9 to -9.1 kcal/mol, respectively. Several hydrogen bonds, including common amino acid residues Lys9 and CYS48, were identified. Molecular dynamics calculations conducted on these potent inhibitors demonstrated their stability throughout a 200 ns simulation, as indicated by metrics such as RMSD, RMSF, Rg, SASA, H-bonds, PCA and FEL analysis. Moreover, PASS analysis and adherence of these natural compounds to drug-likeness rules like Lipinski's further strengthen their candidacy. Considering these calculations and various parameters, these three prominent natural compounds emerge as promising candidates for anti-IL-8 therapy in the management of cancer.Communicated by Ramaswamy H. Sarma