Synthesis and biological evaluation of quinazoline and quinoline bearing 2,2,6,6-tetramethylpiperidine-N-oxyl as potential epidermal growth factor receptor(EGFR) tyrosine kinase inhibitors and EPR bio-probe agents

4-anilinoquinazoline and 4-anilinoquinoline scaffolds bearing a 2,2,6,6-tetramethylpiperidine-N-oxyl(TEMPO) have been synthesized and evaluated for their ability to inhibit EGFR tyrosine kinase and A431 cell lines. Compared to their corresponding parent compounds, all of the new compounds bearing a TEMPO showed more efficient inhibition for EGFR and A431 cells. Furthermore, we have proved that these molecules bearing a TEMPO can exactly get into A431 cells exerting inhibitory effect that may be used for EPR detecting. In our docking model, quinazolines bearing a TEMPO on either 6- or 3-positions took different linking modes according to EGFR crystal structure. In contrast to their parent compounds, these new TEMPO-derived analogues possessed compatible inhibitory effect that might be useful as potential EGFR inhibitors and as EPR bio-probes.