A Novel Conjugate of Bis[((4-bromophenyl)amino)quinazoline],a EGFR-TK Ligand, with a Fluorescent Ru(II)-Bipyridine Complex ExhibitsSpecific Subcellular Localization in Mitochondria

The Epidermal Growth Factor Receptor (EGFR) is a key target in anticancer research, whose aberrant function in malignancies has been linked to severe irregularities in critical cellular processes, including cell cycle progression, proliferation, differentiation and survival. EGFR mutant variants, either transmembrane or translocated to the mitochondria and/or the nucleus, often exhibit resistance to EGFR inhibitors. The ability to non-invasively image and quantify EGFR provides novel approaches in the detection, monitoring and treatment of EGFR-related malignancies. The current study aimed to deliver a new theranostic agent that combines fluorescence imaging properties with EGFR inhibition. This was achieved via conjugation of a in house-developed ((4-bromophenyl)amino)quinazoline inhibitor of mutant EGFR-TK, selected from a focused aminoquinazoline library, with a [Ru(bipyridine)3]2+ fluorophore. A triethyleneglycol-derived diamino linker featuring (+)-ionizable sites was employed to link the two functio...