Design, synthesis and biological activity studies of novel EGFR kinase inhibitor compounds containing benzimidazole ring

Lung cancer remains one of the leading causes of cancer-related deaths globally, with non-small cell lung cancer (NSCLC) representing most cases. Targeting the epidermal growth factor receptor (EGFR) has become a promising therapeutic strategy for NSCLC, as EGFR plays a critical role in tumor growth and progression. In this doctorate thesis, was performed the design, synthesis, and biological evaluation of a new series of benzimidazole/morpholine derivatives with potential EGFR inhibitory and anticancer activity. Gefitinib was selected as the starting compound and various structural modifications were applied to increase biological activity. The synthesized compounds were structurally characterized using 1H-NMR, 13C-NMR, and high-resolution mass spectrometry (HRMS). Their anticancer efficacy was evaluated via MTT assay against the A549 and MCF-7 cell lines. Among the synthesised compounds, 5d, 5e, 5h, and 5i exhibited high anticancer activity in A549 cells. Furthermore, in silico studies have shown that the most active compounds form important hydrogen bonds for EGFR enzyme inhibition.