Partialsynthese maßgeschneiderter Photosensibilisatoren vom Chlorintyp und Studien zur pharmazeutischen Anwendung in der Photodynamischen Therapie

Abstract

Photodynamic therapy is still in its initial stages. Non-acceptance in clinical application so far is due to the need for appropriate photosensitizers fulfilling several requirements. However, in the present state of research, amphiphilic chlorins without charges or ionic moieties are the most promising chromophores. Partial water-solubility or solubility in physiological solvents is important for a clinical application. This thesis deals with the synthesis of chlorin-carbohydrate-amides of various degrees of hydrophilicity, followed by the investigation of their photophysical and bio-medical properties. The synthesis is based on Deuteroporphyrin, which can be converted into chlorins with different alkyl chains by partial synthesis. Another approach is based on the substitution of the chromophores of chlorin e6 and its derivatives. Consequently, the carboxylic moieties were amidated successfully with acyclic sugar amines. The solubility of these amides ranges from moderate to good water-solubility. For all derivatives photophysical measurements showed enhanced absorption qualities compared to those of Photofrin, the currently best reviewed and medically most applied photosensitizer.