MULTI-TARGET OSTEOARTHRITIS PATHWAY ANALYSIS OF FEBRIFUGINE AND HALOFUGINONE USING NETWORK PHARMACOLOGY AND MOLECULAR DOCKING APPROACHES
Osteoarthritis is a progressive joint disorder marked by cartilage degeneration, chronic inflammation, anddysregulated extracellular-matrix turnover, necessitating multi-target therapeutic strategies. Febrifugine andHalofuginone, two quinazolinone-derived alkaloids, have drawn interest for immunomodulatory and antifibroticactivities relevant to osteoarthritic pathology. This study employed an integrated network-pharmacology frameworkto explore their putative molecular landscape in osteoarthritis. Candidate targets were compiled frompublicchemogenomic resources and intersected with osteoarthritis-associated proteins, yielding 29 shared targets for bothcompounds. Protein–protein interaction analysis highlighted central regulatory hubs (AKT1, MMP9, TGFB1, SMAD3, MTOR, TP53, and TNF) implicated in cell-survival signalling, inflammatory cascades, matrix remodelling, and fibrotic responses. Gene Ontology and KEGG enrichment pointed to pathways governing growth-factor signalling, kinase regulation, apoptosis, cytokine activity, and proteolysis of extracellular components, therebyaligning the predicted target set with core osteoarthritis mechanisms. These systems-level results were usedtoprioritise AKT1, MMP9, and TGFB1 as primary nodes for subsequent structure-based evaluation. Molecular docking is planned to quantify binding poses and intermolecular interactions against these targets; however, quantitative docking scores and detailed interaction maps are not reported here because the correspondingsimulations are not yet available. Consequently, the present contribution should be interpreted as hypothesis- generating evidence that rationally narrows the search space toward kinase, metalloproteinase, and TGF-β signallingaxes. Taken together, the network-pharmacology findings nominate Halofuginone and Febrifugine as promisingscaffolds for multi-pathway modulation in osteoarthritis and provide a transparent, reproducible rationale for forthcoming docking analyses, which will further refine mechanistic hypotheses for preclinical evaluation.
Readers around the world
