Navigation/Menü: Links auf weitere Seiten dieser Website
Objekt-Metadaten
| Surface-Functionalized Dendrimers with Potential Application for Anticancer-Therapy Müller, Stephan |
| Haupttitel | Surface-Functionalized Dendrimers with Potential Application for Anticancer-Therapy |
| Titelzusatz | Synthesis and in vitro Cytotoxicity |
| Titelvariante | Oberflächenfunktionalisierte Dendrimere als Wirkstoffträger für die Krebstherapie |
| Zusatz zur Titelvariante | Synthese und in vitro Cytotoxizität |
| Autor | Müller, Stephan
Geburtsort: Koblenz, Deutschland |
| Gutachter | Prof. Dr. Arnulf Dieter Schlüter |
| weitere Gutachter | Prof. Dr. Jürgen-H. Fuhrhop |
| Freie Schlagwörter | Dendrimer, Drug Delivery, OEG, Platinated, orthogonality |
| DDC | 570 Biowissenschaften; Biologie |
| Zusammenfassung | The aim of the present work was to accomplish a synthetic contribution for the application of dendrimers as carriers for anticancer-therapy. A synthetic concept had to be developed, which allows peripheral functionalization of poly(amidoamine)-dendrimers with pharmacologically relevant motifs. The dendrimers were to be equipped with chelating ligands for Pt2+-complexation and were intended to have enhanced solubility in water through OEGs. In order to further optimize the carrier-concept, initial structure/ toxicity correlations were to be evaluated by in vitro cytotoxicity essays. A set of molecules for surface-modification of amino-terminated G0- and G1-dendrimers was synthesized. G0-dendrimers were made accessible, which were based on a trifunctional core moiety. The well-defined construction of bi- (hetero-) functional G1-dendrons and G1-dendrimers was achieved by optimized reaction conditions for the synthesis of tris-orthogonally protected branching units. The compounds with selectively addressable functional groups and monodisperse OEGs ("caps") were equipped with chelating malonic acid or ethylene-diamine ligands or with a fluorescence tag. Their acid group offered the possibility for assembly with dendritic building blocks by employing amide coupling-protocols. The enhanced solubility of "caps" in water was ensured by 12 repeating units of ethylene glycol. The applied coupling protocols made G0-dendrimers 78, 81, 82, 84 and 115 accessible in very good yields and high purity. These molecules served as "models" for this pharmacologically oriented project. The G1-Dendrimers 99 und 100 with ethylene-diamine ligands were obtained in excellent yields in a quasi-convergent approach. Dendrimer 113, carrying fluorescence tag and malonic acid ligands, was readily available and was synthesized in a divergent approach. Dendrimers 81 and 113 are very promising, because they offer free malonic acids for hydrolytically reversible Pt2+-binding. Initial experiments were done to complex these dendrimers with Pt2+. 1H- and 13C-NMR spectroscopy as well as UV-spectra of the obtained compounds, give reason to believe in a successful platination. Unfortunately, corresponding 195Pt-NMR spectrocopic measurements were of minor success, as of yet. Results from cytotoxicity essays on human breast cancer cell lines MCF-7 lead to preliminary, but not generally established structure/ toxicity correlations. None of the dendrimers tested in this context proved to be cytotoxic. In consequence, neither the applied surface-functionalization nor the intrinsic structure of dendrimers of both generations seemed to play a significant role. This can be considered an encouraging signal for the continued development of the described strategy on the generation of new drug-carriers. |
| Dokumente |
FUDISS_derivate_000000001331
Falls Ihr Browser eine Datei nicht öffnen kann, die Datei zuerst herunterladen und dann öffnen.
|
| Fachbereich/Einrichtung | FB Biologie, Chemie, Pharmazie |
| Erscheinungsjahr | 2004 |
| Dokumententyp/-Sammlungen | Dissertation |
| Medientyp/Format | Text |
| Sprache | Englisch |
| Rechte | Nutzungsbedingungen |
| Tag der Disputation | 10.09.2004 |
| Erstellt am | 17.09.2004 - 00:00:00 |
| Letzte Änderung | 19.02.2010 - 14:06:43 |
| Alte Darwin URL | http://www.diss.fu-berlin.de/2004/242/ |
| Statische URL | http://www.diss.fu-berlin.de/diss/receive/FUDISS_thesis_000000001331 |
| URN | urn:nbn:de:kobv:188-2004002422 |
| Zugriffsstatistik | |
