Metabolomics and network pharmacology approach to identify potential bioactive compounds from Trichoderma sp. against oral squamous cell carcinoma

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This study aimed to profile metabolites from five Trichoderma strains and assess their cytotoxic and pharmacological activities , particularly targeting oral squamous cell carcinoma (OSCC). UHPLC-TOF-MS analysis revealed the presence of 25 compounds, including heptelidic acid , viridiol isomers, and sorbicillinol from the different Trichoderma extracts. Pharmacokinetic analysis showed moderate permeability and low interaction with P-glycoprotein, suggesting good drug absorption with minimal interference in cellular uptake. ADME-Tox analysis indicated limited inhibition of cytochrome P450 enzymes, low renal clearance , which are favorable for maintaining therapeutic levels. Toxicity predictions revealed some compounds with potential mutagenicity , but low hepatotoxicity and skin sensitization risks. Network pharmacology identified MAPK1 as a key target for oral cancer, and molecular docking and induced fit docking studies demonstrated strong binding affinities of Trichoderma metabolites, including stachyose and harzianol, to MAPK1 . In addition, molecular dynamics (MD) simulations confirmed stable interactions. In vitro studies on NIH3T3 and YD-10B cells showed significant cytotoxicity, particularly with extracts CNU-05–001 (IC 50 :10.15 µg/mL) and CNU-02–009 (10.00 µg/mL) against YD-10B cells. These findings underscore the potential of Trichoderma metabolites in drug discovery , particularly for cancer therapies.