title: Formation of protoporphyrin IX from carboxylic- and amino-derivatives of 5-aminolevulinic acid.
abstract: BACKGROUND
  Stability of ALA is an important factor for photodynamic therapy (PDT). The dimerization of ALA to pyrazines takes place via the amine group. It is, therefore, to be expected that blocking this group by addition of a formyl group should result in a more stable compound.
  
  
  METHODS
  The ability of a new N-formyl derivative of ALA (N-f-ALA) to form protoporphyrin IX (PPIX) was compared with that of ALA and three of its ester (methyl, butyl and hexyl) derivatives. Dark toxicity of the compounds was measured using MTT assay. Formation of PPIX was measured by fluorescence spectroscopy.
  
  
  CONCLUSIONS
  N-f-ALA showed an outstanding stability in water solutions even at pH 7. However, it induced no PPIX neither in WiDr cells in vitro, nor in mouse skin in vivo. A probable reason is lack of an enzyme that can cleave the bond between the formyl group and ALA. Thus, steric hindrance may prevent processing of the compound into porphobilinogen. N-f-ALA did not inhibit PpIX formation from ALA and is unable to enter the heme cycle. Generation of ALA from its derivatives, therefore, seems to be an essential step in PPIX synthesis.
authors.affiliation: Department of Radiation Biology, Institute for Cancer Research, 0310 Montebello, Oslo, Norway; Institute of Optoelectronics, Military University of Technology, ul. Kaliskiego 2, 00-908 Warsaw, Poland.
authors.forename: Miron
authors.initials: M
authors.lastname: Kaliszewski
authors.affiliation: Department of Radiation Biology, Institute for Cancer Research, 0310 Montebello, Oslo, Norway.
authors.forename: Asta
authors.initials: A
authors.lastname: Juzeniene
authors.affiliation: Department of Radiation Biology, Institute for Cancer Research, 0310 Montebello, Oslo, Norway.
authors.forename: Petras
authors.initials: P
authors.lastname: Juzenas
authors.affiliation: Institute of Optoelectronics, Military University of Technology, ul. Kaliskiego 2, 00-908 Warsaw, Poland.
authors.forename: Miroslaw
authors.initials: M
authors.lastname: Kwasny
authors.affiliation: Industrial Chemistry Research Institute, ul. Rydygiera 8, 01-793 Warsaw, Poland.
authors.forename: Jaroslaw
authors.initials: J
authors.lastname: Kaminski
authors.affiliation: Industrial Chemistry Research Institute, ul. Rydygiera 8, 01-793 Warsaw, Poland.
authors.forename: Zbigniew
authors.initials: Z
authors.lastname: Dabrowski
authors.affiliation: Industrial Chemistry Research Institute, ul. Rydygiera 8, 01-793 Warsaw, Poland.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Golinski
authors.affiliation: Department of Radiation Biology, Institute for Cancer Research, 0310 Montebello, Oslo, Norway.
authors.forename: Johan
authors.initials: J
authors.lastname: Moan