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Synthesis, Properties and In Vitro Photodynamic Activity of Water-soluble Azaphthalocyanines and Azanaphthalocyanines

Authors

  • Petr Zimcik,

    Corresponding author
    1. Department of Pharmaceutical Chemistry and Drug Control, Faculty of Pharmacy in Hradec Kralove, Charles University in Prague, Hradec Kralove, Czech Republic
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  • Miroslav Miletin,

    1. Department of Pharmaceutical Chemistry and Drug Control, Faculty of Pharmacy in Hradec Kralove, Charles University in Prague, Hradec Kralove, Czech Republic
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  • Hana Radilova,

    1. GENERI BIOTECH s.r.o., Hradec Kralove, Czech Republic
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  • Veronika Novakova,

    1. Department of Pharmaceutical Chemistry and Drug Control, Faculty of Pharmacy in Hradec Kralove, Charles University in Prague, Hradec Kralove, Czech Republic
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  • Kamil Kopecky,

    1. Department of Pharmaceutical Chemistry and Drug Control, Faculty of Pharmacy in Hradec Kralove, Charles University in Prague, Hradec Kralove, Czech Republic
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  • Jaroslav Svec,

    1. Department of Pharmaceutical Chemistry and Drug Control, Faculty of Pharmacy in Hradec Kralove, Charles University in Prague, Hradec Kralove, Czech Republic
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  • Emil Rudolf

    1. Department of Medical Biology and Genetics, Faculty of Medicine in Hradec Kralove, Charles University in Prague, Hradec Kralove, Czech Republic
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*Corresponding author email: petr.zimcik@faf.cuni.cz (Petr Zimcik)

Abstract

In this work zinc azaphthalocyanines (AzaPcs) from the group of tetrapyrazinoporphyrazines and zinc azanaphthalocyanines from the group of tetra[6,7]quinoxalinoporphyrazines (TQP) with eight diethylaminoethylsulfanyl substituents were synthesized. Tertiary amines were later quaternized with ethyl iodide to obtain water-soluble photosensitizers (PSs). Quaternized compounds showed high singlet oxygen quantum yields as determined in DMF by monitoring decomposition of 1,3-diphenylisobenzofuran. In water medium, quaternized AzaPc derivatives appeared in monomeric form in a wide range of concentrations while quaternized TQP derivatives showed aggregation at higher concentrations (over 1 μm). Photodynamic activity was tested on Hep2 cells using light of λ > 640 nm. Both quaternized dyes showed high photodynamic activity (IC50 = 104 and 220 nm for AzaPc and TQP, respectively). Dark toxicity was not detected even at the highest concentration used in in vitro tests (200 μm) which indicates a promising therapeutic index of these new substances. Tested compounds localized inside the cells mainly within the lysosomes thus suggesting an endocytic mechanism of cellular uptake. No localization within mitochondria was detected. A great advantage of TQP derivatives over other PSs is their very strong absorption at 747 nm that allows activation at wavelengths penetrating deeper into human tissues.

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