Synthesis and Biological Activity of 3,9-Diazatetraasteranes as Novel EGFR Tyrosine Kinase Inhibitors

Epidermal growth factor receptor (EGFR) kinase is a promising target for the development of novel anticancer drugs. Based on the structure-activity relationships for the known inhibitors, 3,9-diazatetraasteranes have been developed as novel EGFR inhibitors. Molecular docking is performed for 3,9-diazatetraasteranes and the known inhibitor Erlotinib, and it suggests that 3,9-diazatetraasteranes are similar to Erlotinib in interactions with the catalytic sites of EGFR. A series of 3,9-diazatetraasteranes has been synthesized by photocyclization of 4-aryl-1,4-dihydropyridines, and their biological activity has been evaluated against A431 and HepG2 cell lines using Erlotinib as a control. Compound 1c exhibits the most potent antiproliferative activity against A431 (IC 50 = 7.37 μM) and HepG2 (IC 50 = 9.81 μM) cell lines compared to positive controls (IC 50 = 8.92 μM and 12.08 μM). The results are indicating that 3,9-diazatetraasteranes may be the promising potential EGFR inhibitors.