EGFR-Targeted Amino Quinoxaline Derivatives as Potential Anticancer Interventions: In Silico Design and in Vitro Evaluations

Abstract

The Epidermal Growth Factor Receptor (EGFR) remains validated therapeutic goalfor Breast Cancer, especially because of its function in signalling pathways that promote tumor development and viability. In the current investigation, a series of newly designed amino quinoxaline derivatives (QN1–QN10) were investigated for their potential EGFR inhibitory and anticancer activities using an integrated in silico and in vitro approach. Molecular docking studies were carried out using Schrödinger Maestro to rate the binding kineticsof the designed compounds with the EGFR tyrosine kinase domain (PDB ID: 4HJO), employing erlotinib as the reference standard. The docking protocol was validated by redockingerlotinib into the active site, confirming the reliability of the methodology. Glide extra-precision (XP) docking revealed favourable binding orientations of selected derivatives within the EGFR catalytic pocket. The cytotoxicity of selected compounds (QN2, QN4, and QN8) was further calculated through MTT assay for human breast cancer cell line MCF-7. The results proved that the cell longevity was decreased in a concentration-dependent way, with erlotinib exhibiting the greatest potency (LC50 = 18.47 µg/mL). Among the synthesized derivatives, QN4 showed relatively higher activity (LC50 = 121.52 µg/mL) than QN2 and QN8.Statistical analysis proved the relevance of the cytotoxic effects observed (p < 0.0001). Overall, the combined computational and biological findings suggest that amino quinoxaline scaffolds indicate potential avenues for enhanced optimization as EGFR-targeted anticancer drugs.