Effects of naphthoquinone scaffold-derived compounds on head and neck squamous cell carcinoma based on network pharmacology and molecular docking.

OBJECTIVES

This study aimed to analyze the effects of naphthoquinone scaffold-derived compounds on head and neck squamous cell carcinoma (HNSCC) using network pharmacology and molecular docking.

METHODS

We screened candidate compounds from the ASINEX database and evaluated their drug likeness and toxicity. They identified 80 compounds with naphthalenone structures, focusing on 1,4-naphthoquinone and 1,2-naphthoquinone scaffolds. The possible targets of these compounds were predicted using databases like SwissTargetPrediction and Similarity Ensemble Approach Database (SEA).

RESULTS

The common targets between the compounds and HNSCC were identified, yielding 65 overlapping targets. A protein-protein interaction (PPI) network was constructed, and 20 hub genes were identified based on centrality metrics. Gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that these compounds' protective effects against HNSCC are associated with cancer-related pathways, such as those in cancer and proteoglycans in cancer. Molecular docking was performed to evaluate the binding affinity between the compounds and hub genes. The results showed that the compounds had strong binding affinities with key targets like MET and TYK2, with binding energies < -5 kcal/mol.

CONCLUSIONS

The study suggests that naphthoquinone derivatives could serve as novel chemotherapy agents for HNSCC, warranting further research for clinical application.