Determination of the Interleukin‐8 Inhibitory Properties of Naringin and Hesperidin Compounds by Molecular Dynamics

Abstract Interleukin‐8 (IL‐8) serves a crucial role in the development of inflammatory diseases and different types of cancers. Emerging clinical view provides the association between interleukin‐8 (IL‐8) and different inflammatory diseases and increased IL‐8 expression triggered the moderate to severe manifestation. The active expression of IL‐8 protein in tumor cells makes them a potential therapeutic target for anticancer and different disease therapy. To find possible phytoconstituents that might inhibit the IL‐8 function, we have used virtual screening in this instance, utilizing an in‐house library retrieved from the ESSential OIL Data Base. The molecular docking method was used to select the first hits based on their binding affinity toward IL‐8. Resulting, we selected naringin and hesperidin two naturally occurring molecules that exhibit drug‐like characteristics with a notable affinity, efficiency, and specificity against the IL‐8 binding site with common key amino acid residues GLY6, THR10, TYR11, GLU46, and CYS48. Furthermore, the PASS analysis was used to identify the biological properties of the selected hits. These two compounds along with apoprotein were subjected to molecular dynamics (MD) simulations and post‐MD trajectory analysis including RMSD, RMSF, Rg , and SASA FEL and MM‐PBSA calculations. Through this integrated in silico approach, it ascertained that the two identified molecules have strong contact with IL‐8 and form stable protein‐ligand complexes that reflect the inhibitory effect of IL‐8 activity. In vitro, in vivo and other ongoing clinical investigations can be used to further assessment of these two compounds as potential IL‐8 inhibitors in the future phase.