Synthesis and Biological Evaluation of 3,9-Dioxatetraasteranes as Potential Inhibitors of Epidermal Growth Factor Receptor

Abstract

Background: Epidermal growth factor receptor (EGFR) is a validated and therapeutically amenable target, and inhibition of the EGFR signaling pathway has emerged as an attractive target for cancer therapy. Methods: The present work was designed to synthesize and evaluate the antiproliferative activity of a novel series of 3,9-dioxatetraasteranes as potential inhibitors of EGFR. All target compounds were evaluated for antiproliferative activity in vitro against A549 and HepG2 cell lines. Results: Among the target compounds, compound B13 displayed the most potent antiproliferative activity against A549 with IC50 = 4.31 μM and HepG2 with IC50 = 6.92 μM. In addition, a molecular docking study was performed to investigate the binding mode and binding capacity with EGFR (PDB code: 1M17). Conclusion: The results indicated that 3,9-dioxatetraasteranes may be promising potential EGFR inhibitors.