Ethylene Glycol and Amino Acid Derivatives of 5-Aminolevulinic Acid as New Photosensitizing Precursors of Protoporphyrin IX in Cells

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 characte...

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Bibliographic Details
Published in:Journal of medicinal chemistry 2000-12, Vol.43 (25), p.4738-4746
Main Authors: Berger, Yann, Greppi, Alain, Siri, Olivier, Neier, Reinhard, Juillerat-Jeanneret, Lucienne
Format: Article
Language:English
Subjects:
Amino Acids - chemistry
Aminolevulinic Acid - analogs & derivatives
Aminolevulinic Acid - chemical synthesis
Aminolevulinic Acid - chemistry
Aminolevulinic Acid - metabolism
Aminopeptidases - metabolism
Animals
Biological and medical sciences
Dipeptides - chemistry
Ethylene Glycols - chemistry
Fluorescence
Glutamyl Aminopeptidase
Humans
Medical sciences
Photoradiation therapy and photosensitizing agent
Photosensitizing Agents - chemical synthesis
Photosensitizing Agents - chemistry
Photosensitizing Agents - metabolism
Protein Precursors - chemical synthesis
Protein Precursors - chemistry
Protein Precursors - metabolism
Protoporphyrins - biosynthesis
Rats
Treatment with physical agents
Treatment. General aspects
Tumor Cells, Cultured
Tumors
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Summary: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.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm000981q