Aims: The G-quadruplex structural motifs of DNA are considered a novel target for drug discovery. As potential compounds, small molecules that selectively target the G-quadruplex structures may be used for therapeutic purposes. The aim of this study was the thermodynamic investigation of copper porphyrazines and phthalocyanine interaction with human telomeric G-quadruplex DNA.
Materials and Methods: In the present experimental study, interaction of an anionic water-soluble phthalocyanine Cu(PcTs) and two cationic water-soluble tetrapyridinoporphyrazines, including [Cu(2,3-tmtppa)] ⁴⁺ and [Cu(3,4-tmtppa)]⁴⁺ complexes with human telomeric G-quadruplex DNA was thermodynamically investigated in different concentrations of Na⁺ and K⁺ cations, using fluorescence spectroscopy. The data were analyzed via the Stern-Volmer plot and the van't Hoff plot.
Findings: Fluorescent intercalator displacement indicated the displacement ability of the complexes with thiazole orange. Stern-Volmer plots of the porphyrazines exhibited a slight positive deviation from a straight line, suggesting both static and dynamic quenching. In addition, the quenching effect of the two porphyrazines was noticeably higher than the phthalocyanine, implying binding of Cu(PcTs) to both forms of the quadruplex was weaker compared to Cu(2,3-tmtppa) and Cu(3,4-tmtppa). Gibbs free energy (∆G) for binding was negative, implying that the interaction between the complexes and the G-quadruplex DNA was favorable thermodynamically.
Conclusion: The binding of copper porphyrazines to G-quadruplex DNA is stronger than copper phthalocyanine, and their binding is favorable thermodynamically. Porphyrazines have potential to be used as anti-cancer compounds and are suitable complexes for pharmaceutical studies.