Development and application of metallo-phthalocyanines as potent G-quadruplex DNA binders and photosensitizers
Ariadna Gil‐Martínez, Adrián Hernández, Cristina Galiana‐Roselló, Sònia López‐Molina, Javier Ortíz, Ángela Sastre‐Santos, Enrique García‐España, Jorge González‐García
Abstract
Abstract Metallo-phthalocyanines ( MPc ) are common photosensitizers with ideal photophysical and photochemical properties. Also, these molecules have shown to interact with non-canonical nucleic acid structures, such as G-quadruplexes, and modulate oncogenic expression in cancer cells. Herein, we report the synthesis and characterisation of two metallo-phthalocyanines containing either zinc ( ZnPc ) or nickel ( NiPc ) in the central aromatic core and four alkyl ammonium lateral chains. The interaction of both molecules with G-quadruplex DNA was assessed by UV–Vis, fluorescence and FRET melting experiments. Both molecules bind strongly to G-quadruplexes and stabilise these structures, being NiPc the most notable G-quadruplex stabiliser. In addition, the photosensitizing ability of both metal complexes was explored by the evaluation of the singlet oxygen generation and their photoactivation in cells. Only ZnPc showed a high singlet oxygen generation either by direct observation or by indirect evaluation using a DPBF dye. The cellular evaluation showed mainly cytoplasmic localization of ZnPc and a decrease of the IC 50 values of the cell viability of ZnPc upon light activation of two orders of magnitude. Graphical abstract