NDLI: Rhenium and technetium complexes bearing quinazoline derivatives: progress towards a $^{99m}Tc$ biomarker for EGFR-TK imaging

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Pietzsch, Hans-jurgen Paravatou-petsotas, Maria Santos, Isabel C. Rey, Ana Bourkoula, Athanasia Santos, I. Kunstler, Jens-uwe Margaritis, Nikos Pirmettis, Ioannis Fernandes, Célia Kraus, Werner Chiotellis, Aris
Description	Author Affiliation: Fernandes C ( Departamento de Química, ITN, Estrada Nacional 10, Sacavém Codex, Portugal.)
Abstract	The quinazoline derivatives (3-chloro-4-fluorophenyl)quinazoline-4,6-diamine (2) and (3-bromophenyl)quinazoline-4,6-diamine (3) were labelled with $^{99m}Tc$ using the “4 + 1” mixed-ligand system $[Tc(NS_{3})(CN-R)]$ and the tricarbonyl moiety $fac-[Tc(CO)_{3}]^{+}.$ In the “4 + 1” approach the technetium(III) is stabilized by a monodentate isocyanide bearing a quinazoline fragment $(L^{1}1,$ $L^{2}2)$ and by the tetradentate tripodal ligand tris(2-mercaptoethyl)-amine $(NS_{3}).$ In the “4 + 1” approach, $^{99m}Tc-labelling$ was performed in a two-step procedure, the complexes $[Tc(NS_{3})(L^{1}1)]$ (7a) and $[Tc(NS_{3})(L^{2}2)]$ (8a) being obtained in about 50–70% yield. In the tricarbonyl approach, the $fac-[Tc(CO)_{3}]^{+}$ unit is anchored by two different monoanionic chelators bearing the quinazoline derivatives (3-chloro-4-fluorophenyl)quinazoline-4,6-diamine (2) and (3-bromophenyl)quinazoline-4,6-diamine (3). Both chelators have a $N_{2}O$ donor atom set, but one contains a pyrazolyl ring $(L^{5}5H)$ and the other contains a pyridine unit $(L^{6}6H).$ In both cases the conjugation of the quinazoline to the chelator was done through the secondary amine of the potentially tridentate and monoanionic chelators , the corresponding $^{99m}Tc-complexes$ (10a, 11a) being obtained in quantitative yield. The identities of the $^{99m}Tc-labelled$ quinazolines (7a, 8a, 10a, 11a) were confirmed by comparison with the HPLC profiles of the analogous Re compounds (7, 8, 10, 11). All these Re complexes were characterized by NMR and IR spectroscopy , elemental analysis and in some cases by MS and X-ray diffraction analysis . In vitro studies indicate that the quinazoline fragments, after conjugation to the cyano group $(L^{1}1,$ $L^{2}2)$ or to the pyrazolyl containing chelator $(L^{5}5H),$ as well as the corresponding Re complexes (7, 8, 10) inhibit significantly the EGFR autophosphorylation and also inhibit A431 cell growth. These two effects were also found for the pyridine-containing chelator $(L^{6}6H)$ and corresponding Re complex (11), although to a lesser extent.
ISSN	14779226
Issue Number	24
e-ISSN	13645447
Journal	Dalton Trans.
Language	English
Publisher	Royal Society of Chemistry
Publisher Date	2008-06-28
Publisher Place	Great Britain (UK)
Access Restriction	Subscribed
Subject Keyword	Biological Markers Metabolism Organotechnetium Compounds Chemistry Quinazolines Receptor, Epidermal Growth Factor Rhenium Carcinoma, Squamous Cell Drug Therapy Pathology Cell Proliferation Drug Effects Chelating Agents Chromatography, High Pressure Liquid Crystallography, X-Ray Epidermal Growth Factor Pharmacology Humans Magnetic Resonance Spectroscopy Models, Molecular Chemical Synthesis Phosphorylation Tumor Cells, Cultured Journal Article Research Support, Non-U.S. Gov't
Content Type	Text
Resource Type	Article
Subject	Inorganic Chemistry

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