Funktionalisierte Inhibitoren der New Permeability Pathways in malariainfizierten Erythrozyten

Zur Behandlung der Infektionskrankheit Malaria sind nur wenige Arzneimittel erhältlich. Auf Grund zunehmender Resistenzentwicklung gegen diese Substanzen, ist es unabdingbar neue Zielstrukturen für künftige Wirkstoffentwicklung zu identifizieren. Wird ein Erythrozyt von einem Malariaparasiten infiz...

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Bibliographic Details
Main Author: Steiner, Iljana Sonja
Contributors: Schlitzer, Martin (Prof. Dr.) (Thesis advisor)
Format: Doctoral Thesis
Language:German
Published: Philipps-Universität Marburg 2016
Subjects:
NPP
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Table of Contents: Against the infectious disease malaria only a very limited number of active agents is available. Growing resistances against these substances urge the need to identify new targets for potential drug-candidates. When a red blood cell (RBC) is infected by a malaria-parasite so called New Permeability Pathways or Novel Permeation Pathways (NPP) are created within the RBC’s membrane and make it permeable to various substances. The molecular structure of the NPP has not yet been identified, but might serve as a new target in drug-discovery. Within this thesis new inhibitors of the NPP of RBCs infected with Plasmodium falciparum were designed, synthesized and tested in the iso-osmotic haemolysis assay. These substances can be categorised into three different classes: Derivatives of biotin, 2-aminobenzoic acid and thiazolidin-2,4-dione. Especially the activity of the thiazolidin-2,4-dione-derivatives proofed to be comparable to the best yet known inhibitors of the NPP (e.g. NPPB). However, each class helped acquire more knowledge about the NPP and the influence of different moieties on NPP-inhibition. Several compounds were designed carrying a fluorescent motive. Their uptake and distribution inside the infected RBCs could therefore be monitored by fluorescence microscopy. The synthesis routes described in this thesis will allow quick access to additional active derivatives. The synthesized compounds can be used for further identification of the molecular structure of the NPP.