Chemical Characterization and Biological Potential of Simarouba glauca Leaf Extract: GC-MS, In vitro, and Molecular Docking Studies

Background: Medicinal plants remain an important source of therapeutic agents due to their rich phytochemical composition and broad pharmacological activities. Simarouba glauca is a traditionally used medicinal plant; however, its leaf extract has not been comprehensively investigated for combined antioxidant, antimicrobial, anticancer, and molecular docking potential against oral cancer targets. Objectives: This study aimed to characterize the phytochemical constituents of ethanolic Simarouba glauca leaf extract and evaluate its antioxidant, antimicrobial, and anticancer activities, supported by molecular docking analysis. Materials and Methods: Dried leaves of S. glauca were extracted using ethanol, and the phytochemical constituents were identified by GC-MS analysis. Antioxidant activity was assessed using DPPH, Nitric Oxide (NO), and Ferric Reducing Antioxidant Power (FRAP) assays. Antimicrobial activity was evaluated against selected bacterial and fungal pathogens using the agar well diffusion method. Cytotoxic activity was determined against human oral cancer KB cells using the MTT assay. To explore the possible anticancer mechanism, major phytocompounds identified by GC-MS were subjected to molecular docking against Cyclin-Dependent Kinase 4 (CDK4), a key regulator of cell-cycle progression. Results: GC-MS analysis identified 23 bioactive phytocompounds in the ethanolic leaf extract. The extract exhibited concentration-dependent antioxidant activity by significantly scavenging DPPH and NO radicals and enhancing ferric reducing power. It also showed notable antimicrobial activity against the tested pathogens. In the MTT assay, the extract significantly decreased KB cell viability in a dose-dependent manner, indicating potent cytotoxic effects. Molecular docking revealed strong binding interactions of selected phytocompounds with the active site of CDK4, suggesting possible inhibition of cancer cell proliferation. Conclusion: Ethanolic Simarouba glauca leaf extract possesses significant antioxidant, antimicrobial, and anticancer properties. The integrated in vitro and in silico findings highlight the therapeutic potential of S. glauca leaves as a promising natural source for the development of novel antimicrobial agents and targeted therapies against oral cancer.