Exploring the anticancer potential of Tinospora cordifolia with computational insights into EGFR inhibition

<i>Tinospora cordifolia</i> is a well-known Ayurvedic medicinal plant with reported immunomodulatory and anticancer properties, yet integrated studies linking its phytochemistry to biological and molecular mechanisms remain limited. In this study, the methanolic extract of <i>T. cordifolia</i> was evaluated for antioxidant and cytotoxic activities, alongside computational investigations of its key phytoconstituents. Spectroscopic analyses (FTIR and UV-Vis) confirmed the presence of functional groups such as amines, phenolics, and aromatic systems. The extract demonstrated notable antioxidant potential and exhibited significant cytotoxicity against Dalton's lymphoma ascites, Ehrlich Ascites Carcinoma, and MCF-7 breast cancer cell lines, with morphological changes suggestive of apoptosis or necrosis. Computational studies using density functional theory and molecular docking highlighted Tinocordiside as the most bioactive compound. Tinocordiside showed favorable frontier molecular orbital properties and strong binding affinity to the EGFR tyrosine kinase domain, forming multiple hydrogen bonds with critical residues and displaying a docking score comparable to Erlotinib. In contrast, despite its promising activity, Tinocordiside's bulky glycosidic structure and poor solubility may limit cellular permeability and bioavailability. This underscores the need for apoptosis marker studies in vitro, <i>in vivo</i> validation, and advanced formulation strategies such as amorphous solid dispersions, lipid-based nanoparticles, or cyclodextrin complexes to enhance its therapeutic potential. In summary, <i>T. cordifolia</i> methanolic extract exhibits potent antioxidant and anticancer activity, with Tinocordiside as a promising EGFR-targeting lead compound for further therapeutic exploration.