Network Pharmacology and Molecular Docking Analysis of GC-MS Identified Compounds from Ethyl Acetate Extract of Kocuria sp. against Oral Cancer

Oral cancer poses a significant global health challenge due to its poor prognosis and limited therapeutic advancements.

This study investigates the therapeutic potential of Kocuria sp. NAT1, a bacterial strain isolated from Pachycondyla sennaarensis collected in Riyadh, Saudi Arabia, for oral cancer treatment. Bacterial isolates were cultured in nutrient broth and metabolites were extracted using ethyl acetate. Identification was conducted using MALDI-TOF MS.

GC-MS analysis identified 39 bioactive compounds, including 2,5-piperazinedione and pyrrolo[1,2-a]pyrazine-1,4-dione. Network pharmacology was employed to assess drug-likeness and target interactions, integrating Swiss ADME and Swiss Target Prediction. Oral cancer-related targets were retrieved from multiple databases and a protein-protein interaction (PPI) network was constructed using STRING and analyzed with Cytoscape. Functional pathway enrichment (GO/KEGG) revealed significant involvement in apoptosis resistance, cancer cell migration and metastasis regulation. Molecular docking using Auto Dock Tools confirmed strong binding affinities of the key bioactive compounds to oncogenic targets, including TNF, SRC, KRAS and EGFR. These findings highlight the potential of Kocuria sp. NAT1-derived metabolites as novel candidates for oral cancer therapy, warranting further in vitro and in vivo validation to explore their clinical applicability.