PHTHALOCYANINE-INDUCED PHOTOHEMOLYSIS: STRUCTURE-ACTIVITY RELATIONSHIP AND THE EFFECT OF FLUORIDE |
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| Authors: | E Ben-Hur Z Malik T M A R Dubbelman P Margakon H Ali J E van Lier |
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| Institution: | Nuclear Research Center-Negev, P.O. Box 9001. Beer-Sheva 84190, Israel;Bar Ilan University, Department of Life Sciences, Ramat-Can, Israel;Sylvius Laboratory, Department of Medical Biochemistry, P.O. Box 9503, 2300 RA Leiden, The Netherlands;Sherbrooke University, Faculty of Medicine, MRC Group in the Radiation Sciences, Sherbrooke, Quebec J1H 5N4, Canada |
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| Abstract: | Abstract— Phthalocyanine (Pc) containing AI, Ga or Zn as central metal ligand and substituted with a varying number of sulfonic acid residues as well as additional benzene rings were synthesized and their photodynamic activity was assayed using photohemolysis of human erythrocytes as an endpoint. The Pc derivatives vaned > 300-fold in their photodynamic activity. Activity corrclated with binding of the dye to the cell, with the exception of some of the amphiphilic dyes where cell uptake was an order of magnitude higher than expected from the observed activity. Fluoride was shown to inhibit AIPcSn-induccd photohemolysis. This effect occurred also with other AlPc and GaPc derivatives, but the concentration of F required to slow photohemolysis by a factor of two (Ki) varied between 4 μ M and 10 mM. Fluorescence spectral studies indicated complex formation between F? and the dye, which was stronger for AlPc than GaPc derivatives. Ultrastructural studies using scanning electron microscopy showed that the photosensitized cells were converted to spherocytes and that F? prevented this to a large extent. |
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