Synthesis and preclinical evaluation of rhenium and technetium-99m “4 + 1” mixed-ligand complexes bearing quinazoline derivatives as potential EGFR imaging agents

Evaluation of Rhenium and Technetium-99m Complexes Bearing Quinazoline Derivatives as Potential EGFR Agents

“…It is also worth mentioning that the metal tricarbonyl core does not significantly modify biological activity. Remarkably, complex 5a presents the highest inhibition of EGFR phosphorylation compared to previously reported [ 10 , 11 , 13 ] similar complexes ( Table 3 ), revealing an overall improvement in their design and indicating that elongation of the spacer between the pharmacophore and the chelator was beneficial for the inhibition activity.…”

“…Previous studies reported by our team [ 10 , 11 , 13 ] have demonstrated that the rhenium complexes with 4-anilinoquinazoline derivatives inhibit phosphorylation and demonstrate high cytotoxicity in the human cancer cells (A431 cell line), which overexpress the epidermal growth factor receptor (EGFR). Therefore, the newly synthesized rhenium complexes and ligands bearing the pharmacophore moiety 3-bromo-4-anilinoquinazoline were also evaluated for their cytotoxic properties, while complex 5a , with the lowest IC 50 value, was evaluated further for its potency to inhibit EGFR phosphorylation.…”

“…The in vitro biological studies were established using the human epidermoid vulvar carcinoma A431 cell line, which overexpresses EGFR. Cells were available in our laboratory from previous studies [ 10 , 11 , 13 ]. Cells were maintained in high glucose D-MEM medium with L-glutamine (PAA Laboratories GmbH, Pasching, Austria) and supplemented with 10% fetal bovine serum (PAA Laboratories GmbH) and penicillin/streptomycin (PAA Laboratories GmbH) 100 UI/100 μg per mL, in 5% CO 2 incubator at 37 °C.…”

“…The inhibition of EGFR phosphorylation was studied as described in the literature [ 13 ]. A431 cells (5 × 10 5 cells/well) were seeded in 6-well plates and incubated for 24 h. Then, the medium was replaced with fresh medium without fetal bovine serum.…”

“…In the majority of the reported 99m Tc-labeled quinazoline derivatives [ 10 , 11 , 12 , 13 ], the 4-anilinoquinazoline pharmacophore was coupled to tailor-made chelators suitable for the stabilization of either the M III (M = Re and 99m Tc) core with a ‘‘4+1′’ mixed-ligand system or the tricarbonyl fac -[M I (CO) 3 ] + core. It was shown that the presence of the organometallic core does not deteriorate the pharmacological properties of the 4-anilinoquinazoline pharmacophore.…”