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  • Phase I and II study of Auranofin in Chronic Lymphocytic

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    Contents lists available at ScienceDirect
    Journal of Inorganic Biochemistry
    journal homepage: www.elsevier.com/locate/jinorgbio
    Binding and photodynamic action of the cationic zinc phthalocyanines with T different types of DNA toward understanding of their cancer therapy activity
    Ewan K.S. McRae, Dustin E. Nevonen, Sean A. McKenna , Victor N. Nemykin
    Department of Chemistry, University of Manitoba, 144 Dysart Rd, R3T 2N2 Winnipeg, MB, Canada
    Keywords:
    Photodynamic therapy
    DNA binding
    Confocal microscopy
    Phthalocyanine
    Singlet oxygen generation 
    Two cationic zinc phthalocyanines have been tested for their interactions with several DNA secondary structures. Despite different aggregation properties, both phthalocyanines bind to DNA in monomeric forms. The strong photodynamic activity of phthalocyanines was demonstrated by in vitro experiments and correlate well with high singlet oxygen yields determined experimentally with 1,3-diphenylisobenzofurane. Both phthalocyanines ac-cumulate in the cell cytoplasm prior to radiation; however, only the octacationic photosensitizer was observed in the cell nuclei after irradiation.
    1. Introduction
    Transition metal phthalocyanines (Pcs) are well known functional dyes used as colorants in industry [1–6], active components in information re-cording devices [7–11], and catalysts [12–16]. It is known that the axially or core-substituted closed-shell Pcs, especially aluminum, silicon, and zinc derivatives, are suitable for applications in photodynamic therapy (PDT) of cancer [17–29]. Indeed, one of the sulfonated aluminum phthalocyanines (AlPcs, also known as Photosense [30,31]) is currently in clinical use in Russia. The key advantages of closed-shell transition metal phthalocyanines for PDT applications lie in their easily tunable optical properties and triplet state formation, which in turn are responsible for effective singlet oxygen production needed for photodynamic action. Recently, studies have been performed on the effectiveness of the polycationic zinc phthalocyanines (ZnPcs) for antimicrobial [32] and anticancer PDT applications [33]; however, unlike in well studied sulfonated AlPc derivatives, very little is known about the binding and photodynamic action of such Pcs with dif-ferent DNA secondary structures [34–36]. Thus, in this paper we discuss the binding and photodynamic activities of two cationic ZnPcs (Pc1 and Pc2, Chart 1) for single-stranded (SS-DNA), double-stranded (DS-DNA), and G-quadruplex DNA (G4-DNA).