Exploring the Therapeutic Potential of Tinospora cordifolia with Computational Insights into EGFR Inhibition

Abstract Tinospora cordifolia (T. cardifolia) is a renowned medicinal plant in Ayurveda, known for its immunomodulatory, antioxidant, and anticancer effects. However, integrated studies combining phytochemical, biological, and molecular docking analyses are limited. This study evaluated the antioxidant and cytotoxic activities of T. cordifolia methanolic extract and investigated its major phytoconstituents using density functional theory (DFT) and molecular docking against the EGFR tyrosine kinase domain.The methanolic extract underwent FTIR and UV–Vis spectroscopy to identify functional groups and electronic transitions. Antioxidant activity was tested via DPPH and hydroxyl radical scavenging assays, showing concentration-dependent effects with IC₅₀ values of 235 µg/mL in both assays. Cytotoxicity against EAC and DLA cell lines was assessed by Trypan Blue exclusion and MTT assays. The extract exhibited strong cytotoxicity, particularly on DLA cells (IC₅₀ = 14.3 µg/mL), compared to EAC cells (IC₅₀ = 58.6 µg/mL), with morphological changes indicating apoptosis or necrosis. FTIR revealed N–H, O–H, C–F, and C–Br groups, indicating amines, phenolics, and halogenated compounds. UV–Vis showed a prominent 290 nm absorption related to π→π* transitions of aromatic systems. DFT calculations (B3LYP/6-311 + + G(d,p)) on berberine, palmatine, magnoflorine, and tinocordiside identified Tinocordiside as the most reactive, with the lowest LUMO energy (–1.66 eV), highest electrophilicity index (3.49 eV), and lowest chemical potential (–4.23 eV). Molecular docking against EGFR (PDB ID: 1M17) showed Tinocordiside formed four hydrogen bonds with key residues and had a Glide score of − 6.72 kcal/mol, close to Erlotinib’s − 7.63 kcal/mol.In summary, T. cordifolia methanolic extract exhibits potent antioxidant and anticancer activity, with Tinocordiside as a promising EGFR-targeting lead compound for further therapeutic exploration.