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 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.
Berger
Y
Y
Institute of Chemistry, Neuchâtel University, avenue de Bellevaux, P.O. Box 2, CH-2007 Neuchâtel, Switzerland.
Greppi
A
A
Siri
O
O
Neier
R
R
Juillerat-Jeanneret
L
L
D000596:Amino Acids / Q000737:chemistry*; D000622:Aminolevulinic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D000626:Aminopeptidases / Q000378:metabolism; D000818:Animals; D004151:Dipeptides / Q000737:chemistry*; D005026:Ethylene Glycols / Q000737:chemistry*; D005453:Fluorescence; D043384:Glutamyl Aminopeptidase; D006801:Humans; D017319:Photosensitizing Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D011498:Protein Precursors / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D011524:Protoporphyrins / Q000096:biosynthesis*; D051381:Rats; D014407:Tumor Cells, Cultured
D000596:Amino Acids; D004151:Dipeptides; D005026:Ethylene Glycols; D017319:Photosensitizing Agents; D011498:Protein Precursors; D011524:Protoporphyrins; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX; D000626:Aminopeptidases; D043384:Glutamyl Aminopeptidase