New quinazoline-N-4-fluorophenyl derivatives as potential anticancer agents: Discovery of a promising dual EGFR/VEGFR-2 inhibitor

This research is dedicated to synthesizing a new group of quinazoline-N-4-fluorophenyl 4a–d structures and evaluating their anticancer efficacy across multiple cancer cell lines. The molecular design of these derivatives was based on the structural features required for dual inhibition of VEGFR-2 and EGFR. The new derivatives were structurally characterised by NMR analyses. Cytotoxicity was assessed in this study against various cancerous cell strains. Among these, the top three products were further assessed for their capacity to block the enzymatic activity of (VEGFR-2) and (EGFR). Product 4b, in particular, exhibited a strong cytotoxic profile, with IC₅₀ values of 68.2 ± 1.54 nM against EGFR and 189 ± 5.66 nM against VEGFR-2. Molecular docking studies demonstrated that compound 4b effectively interacts with the active sites of both VEGFR-2 and EGFR, potentially influencing its action pathway as a powerful inhibitor.