A versatile water soluble ball-type phthalocyanine as potential antiproliferative drug: the interaction with G-quadruplex formed from Tel 21 and cMYC

G-quadruplexes are biologically important DNA conformations exist generally in guanine rich segments of DNA, such as telomere and proto-oncogene. The formation of these secondary structures is thought to inhibit the expression of certain genes, such as the inhibition of telomerase. The inhibition of telomerase and suppression of a specific gene expression are important approaches for interruption of cancer cell's proliferation. In the present study, the effect of a versatile water soluble ball-type phthalocyanine on G-quadruplex formation and stabilization was investigated to demonstrate its potential usage in cancer chemotherapy. Two important guanine rich oligomers, cMYC and Tel 21 were used as G-quadruplex former sequence. To the best of our knowledge, this is the first study about the interaction of a ball-type phthalocyanine with G-quadruplex structures.  The interactions of the compound with G-quadruplex molecules were monitored spectrophotometrically. The structural differentiations of G-quadruplex after binding were investigated with circular dichroism spectrophotometry. The replacement ability of the molecule with a known DNA binding molecule, ethidium bromide, was clarified fluorometrically. The Stern-Volmer studies were conducted for determination of the quenching mechanism. The strong interaction of the molecules (ball-type phthalocyanine with oligomer) showed us the potential usage of these drug conjugates for targeted photodynamic therapy in the future. 

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  • 1 A. Ali, S. Bhattacharya, DNA binders in clinical trials and chemotherapy, Bioorganic Med. Chem. 22 (2014) 4506–4521.
  • 2 M. Di Antonio, R. Rodriguez, S. Balasubramanian, Experimental approaches to identify cellular G-quadruplex structures and functions, Methods. 57 (2012) 84–92.
  • 3 H. Han, L.H. Hurley, G-quadruplex DNA: A potential target for anti-cancer drug design, Trends Pharmacol. Sci. 21 (2000) 136–142.
  • 4 A.J. Bhattacharjee, K. Ahluwalia, S. Taylor, O. Jin, J.M. Nicoludis, R. Buscaglia, et al., Induction of G-quadruplex DNA structure by Zn(II) 5,10,15,20-tetrakis(N-methyl-4-pyridyl)porphyrin, Biochimie. 93 (2011) 1297–1309.
  • 5 T.A. Brooks, L.H. Hurley, Targeting MYC Expression through G-Quadruplexes, Genes Cancer. 1 (2010) 641–649.
  • 6 D.S.H. Chan, H. Yang, M.H.T. Kwan, Z. Cheng, P. Lee, L.P. Bai, et al., Structure-based optimization of FDA-approved drug methylene blue as a c-myc G-quadruplex DNA stabilizer, Biochimie. 93 (2011) 1055–1064.
  • 7 V. Dapic, Biophysical and biological properties of quadruplex oligodeoxyribonucleotides, Nucleic Acids Res. 31 (2003) 2097–2107.
  • 8 J. Moon, J.H. Han, D.Y. Kim, M. Jung, S.K. Kim, Effects of deficient of the Hoogsteen base-pairs on the G-quadruplex stabilization and binding mode of a cationic porphyrin, Biochem. Biophys. Reports. 2 (2015) 1–7.
  • 9 E.W. White, Selective Recognition of Quadruplex DNA by Small Molecules by, (2006).
  • 10 T. Simonsson, G-quadruplex DNA structures - Variations on a theme, Biol. Chem. 382 (2001) 621–628.
  • 11 C. Gao, W. Zhang, S. He, S. Li, F. Liu, Y. Jiang, Synthesis and antiproliferative activity of 2,7-diamino l0-(3,5-dimethoxy)benzyl-9(10H)-acridone derivatives as potent telomeric G-quadruplex DNA ligands, Bioorg. Chem. 60 (2015) 30–36.
  • 12 A. De Cian, L. Lacroix, C. Douarre, N. Temime-Smaali, C. Trentesaux, J.-F. Riou, et al., Targeting telomeres and telomerase, Biochimie. 90 (2008) 131–155.
  • 13 L. Zhang, J. Huang, L. Ren, M. Bai, L. Wu, B. Zhai, et al., Synthesis and evaluation of cationic phthalocyanine derivatives as potential inhibitors of telomerase, Bioorganic Med. Chem. 16 (2008) 303–312.
  • 14 P. Charoenphol, H. Bermudez, Design and application of multifunctional DNA nanocarriers for therapeutic delivery, Acta Biomater. 10 (2014) 1683–1691.
  • 15 E. Yabaş, E. Bağda, E. Bağda, The water soluble ball-type phthalocyanine as new potential anticancer drugs, Dye. Pigment. 120 (2015) 220–227.
  • 16 G. De Torre, G. Bottari, U. Hahn, T. Torres, Functional Phthalocyanine Molecular Materials, 2010.
  • 17 A.Y. Tolbin, A. V. Ivanov, L.G. Tomilova, N.S. Zefirov, Preparation of 1,2-bis(3,4-dicyanophenoxymethyl)benzene and the binuclear zinc phthalocyanine derived from it, Mendeleev Commun. 12 (2002) 96–97.
  • 18 L. Hassani, F. Hakimian, E. Safaei, Spectroscopic investigation on the interaction of copper porphyrazines and phthalocyanine with human telomeric G-quadruplex DNA, Biophys. Chem. 187–188 (2014) 7–13.
  • 19 A.A. Salem, I.A. El Haty, I.M. Abdou, Y. Mu, Interaction of human telomeric G-quadruplex DNA with thymoquinone: A possible mechanism for thymoquinone anticancer effect., Biochim. Biophys. Acta. 1850 (2015) 329–42.
  • 20 H. Yaku, T. Murashima, H. Tateishi-Karimata, S.I. Nakano, D. Miyoshi, N. Sugimoto, Study on effects of molecular crowding on G-quadruplex-ligand binding and ligand-mediated telomerase inhibition, Methods. 64 (2013) 19–27.
  • 21 V. Kumar, A. Sengupta, K. Gavvala, R.K. Koninti, P. Hazra, Spectroscopic and thermodynamic insights into the interaction between proflavine and human telomeric G-quadruplex DNA., J. Phys. Chem. B. 118 (2014) 11090–9.
  • 22 S. Neidle, M. a Read, G-quadruplexes as therapeutic targets., Biopolymers. 56 (2001) 195–208.
  • 23 S. Neidle, Genomic Quadruplexes as Therapeutic Targets, Ther. Appl. Quadruplex Nucleic Acids. (2012) 119–138.
  • 24 D. Ren iuk, I. Kejnovska, P. kolakova, K. Bedna ova, J. Motlova, M. Vorli kova, Arrangements of human telomere DNA quadruplex in physiologically relevant K+ solutions, Nucleic Acids Res. 37 (2009) 6625–6634.
  • 25 H. a Benesi, J.H. Hildebrand, A spectrophotometric investigation of the interaction of iodine with aromatic hydrocarbons, J. Am. Chem. Soc. 71 (1949) 2703–2707.
  • 26 H. Dezhampanah, T. Darvishzad, M. Aghazadeh, Thermodynamic and spectroscopic study on the binding of interaction anionic phthalocyanine with calf thymus DNA, Spectrosc. An Int. J. 26 (2011) 357–365.
  • 27 J. Jaumot, R. Gargallo, Experimental Methods for Studying the Interactions between G-Quadruplex Structures and Ligands, Curr. Pharm. Des. 18 (2012) 1900–1916.
  • 28 M. Sirajuddin, S. Ali, A. Badshah, Journal of Photochemistry and Photobiology B : Biology Drug – DNA interactions and their study by UV – Visible , fluorescence spectroscopies and cyclic voltametry, J. Photochem. Photobiol. B Biol. 124 (2013) 1–19.
  • 29 S. Paramasivan, I. Rujan, P.H. Bolton, Circular dichroism of quadruplex DNAs: Applications to structure, cation effects and ligand binding, Methods. 43 (2007) 324–331.
  • 30 M. Islam, S. Fujii, S. Sato, T. Okauchi, S. Takenaka, A Selective G-Quadruplex DNA-Stabilizing Ligand Based on a Cyclic Naphthalene Diimide Derivative, Molecules. 20 (2015) 10963–10979.
  • 31 Q. Guo, M. Lu, L. a Marky, N.R. Kallenbach, Interaction of the dye ethidium bromide with DNA containing guanine repeats., Biochemistry. 31 (1992) 2451–2455.
  • 32 F. Koeppel, J.F. Riou, a Laoui, P. Mailliet, P.B. Arimondo, D. Labit, et al., Ethidium derivatives bind to G-quartets, inhibit telomerase and act as fluorescent probes for quadruplexes., Nucleic Acids Res. 29 (2001) 1087–1096.