Entwicklung metallorganischer Enzyminhibitoren für Histondeacetylasen und Carboanhydrasen
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Philipps-Universität Marburg
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Abstract
The development of new chemical compounds as synthetic therapeutics for biological systems is an important field of medicinal chemistry. Most clinically used substances are purely organic compounds, while metals are preferred classical tools in nuclear medicine. Bioorganometallic chemistry, a combination of bioinorganic and organometallic chemistry, represents a rapidly growing field within chemical biology. Meggers et al. have investigated the application of chemically inert organometallic complexes as kinase inhibitors, where the metal has only a structural function. Through varying the ligands around the metal center it is possible to generate rigid structures that fill the enzyme pocket in a unique fashion and overcome the limited tetrahedral geometry of classic organic compounds. The principal purpose of this dissertation was to demonstrate the generality of this design strategy of using metal complexes as enzyme inhibitors for other protein targets. For this approach, histone deacetylases and carbonic anhydrases were chosen. Several broad-spectrum inhibitors, with related structural motifs for each enzyme class, were used as templates for the development and synthesis of bidentate pharmacophore ligands. These ligands were used to prepare a small library of metal complexes, which were subsequently tested for their biological activity. Overall, the results contained in this dissertation demonstrate the potential of metal complexes as potent inhibitors of histone deacetylases and carbonic anhydrases. This is a promising starting point for development of further isoform selective compounds.
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Created: 2012Issued: 2013-02-22Updated: 2013-02-22
Faculty
Fachbereich Chemie
Publisher
Philipps-Universität Marburg
Language
ger
Data types
DoctoralThesis
Keywords
Metal ComplexesCAHDACOrganometallic CompoundsCarbonic AnhydraseEnzyme InhibitorBioorganometallchemieHistone Deacetylase
DFG-subjects
Histon-DeacetylaseMetallorganische VerbindungenMetallkomplexeCarboanhydraseIridiumEnzyminhibitorRuthenium
DDC-Numbers
540
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Ritterbusch, Florian: Entwicklung metallorganischer Enzyminhibitoren für Histondeacetylasen und Carboanhydrasen. : Philipps-Universität Marburg 2013-02-22. DOI: https://doi.org/10.17192/z2012.1107.
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This item has been published with the following license: In Copyright