In Silico study of Potent Polyphenolic Phytochemicals as Natural Inhibitors against Kinase Enzymes in Breast and Lung Cancer

In this study, a library of 80 structurally diverse phytochemicals, primarily polyphenolic compounds, was computationally screened for potential anti-breast and anti-lung cancer activity. Using a comprehensive in silico approach comprising ADMET profiling, Quantitative Structure-Activity Relationship (QSAR) modeling, molecular docking, and molecular dynamics (MD) simulations, we evaluated the interaction of these compounds with key cancer-associated kinase enzymes: EGFR and CDK2 The majority of the compounds met favourable pharmacokinetic criteria and fell into toxicity class 4 or higher, indicating acceptable safety profiles. Among the candidates, Hinokiflavone and Isotretinoin emerged as the top-performing ligands against EGFR and CDK2, respectively. Molecular Dynamics Simulation and binding energy analysis revealed a notable binding affinity of Isotretinoin in case of CDK2 inhibitor than Tamoxifen, a standard reference anticancer drug, while Hinokiflavone showed slightly lower affinity. The findings suggest that Isotretinoin and Hinokiflavone demonstrated a favorable interactional analysis with EGFR and CDK2 in computational analysis, suggesting as potential anti-cancer candidates. However, experimental validation is required to confirm their biological activity.