Ethylene Glycol and Amino Acid Derivatives of 5-Aminolevulinic Acid as New Photosensitizing Precursors of Protoporphyrin IX in Cells
| Autor: | Lucienne Juillerat-Jeanneret, Olivier Siri, Alain Greppi, Reinhard Neier, Yann Berger |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
medicine.medical_treatment
Protoporphyrins Photodynamic therapy Glutamyl Aminopeptidase Aminopeptidases Fluorescence chemistry.chemical_compound Drug Discovery Tumor Cells Cultured medicine Animals Humans Amino Acids Protein Precursors Cytotoxicity chemistry.chemical_classification Photosensitizing Agents Dipeptide Protoporphyrin IX Aminolevulinic Acid Dipeptides Photosensitizing Agent Rats Amino acid chemistry Biochemistry Molecular Medicine Ethylene Glycols Protoporphyrin Ethylene glycol |
| Zdroj: | Journal of Medicinal Chemistry. 43:4738-4746 |
| ISSN: | 1520-4804 0022-2623 |
| DOI: | 10.1021/jm000981q |
| Popis: | Protoporphyrin IX (PpIX) is used as a photosensitizing agent in photodynamic detection and therapy (PDT) of cancer and is synthesized intracellularly from aminolevulinic acid (ALA) precursors. To evaluate means to specifically target ALA derivatives to defined cells, we have synthesized and characterized ethylene glycol esters and amino acid pseudodipeptide derivatives of ALA as potential specific substrates for cellular esterases and aminopeptidases, respectively. The PpIX formation induced by these products was investigated using cultures of human and rat cell lines of carcinoma and endothelial origins. The cytotoxicity of these compounds in the absence of light was also controlled. The results have shown that ethylenglycol esters can induce high levels of PpIX and are useful at concentrations below their cytotoxicity threshold. From the ALA-amino acid derivatives which were evaluated, the highest PpIX production was obtained using ALA derivatives of neutral amino acids, as compared to acidic or basic amino acids. |
| Databáze: | OpenAIRE |
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