Abstract
This computational work uses ligand-based virtual screening and molecular docking simulations to uncover and characterize anti-inflammatory flavones. Flavones with experimental validation and anti-inflammatory activities were chosen for the investigation. The three-dimensional structure of Janus kinase (JAK) from Protein Data Bank (PDB) was extensively processed to ensure its quality and reliability. R and R-free values, bond angle, and length RMS Zscore were assessed before and after crystallographic refinement using PDB-REDO. Multiple methods confirmed the protein model’s quality and dependability. SwissSimilarity, a web tool for ligand-based virtual screening, revealed 400 possible interactions, 10 of which were from virtual compound libraries. CB-Dock molecular docking simulations with detailed interaction visualization demonstrated strong binding affinities between particular flavones and JAK. ADMETTox confirmed the flavones’ safety and drug-likeness. One interesting candidate was CHEMBL1779470, which had great water solubility, moderate lipophilicity, and good physicochemical qualities. The drug had minimal GI absorption, was not a P-gp substrate or BBB permeant, and did not inhibit the primary cytochrome P450 enzymes. Toxicity models show that CHEMBL1779470 is not organ-damaging, carcinogenic, immunological, mutagenic, or cytotoxic. However, it affected nuclear receptor signalling pathways, suggesting impacts on AhR and ER. The computational results show that CHEMBL1779470 is a flavone with high JAK binding, drug-like properties, and expected safety. This supports experimental verification and research of CHEMBL1779470 as an inflammatory disease therapy.
Keywords: Flavones, Janus kinase inhibitors, Computational exploration, Ligand-based virtual screening, Molecular docking and inflammatory disorders.