Is Silver a Precious Metal for G-Quadruplex Stabilization Mediated by Porphyrins?

Cancer is a leading cause of death, so continuous efforts into cancer therapy are imperative. In tumor cells, telomerase and oncogene activity are key points for uncontrolled cell growth. Targeting these processes with ligands that inhibit telomerase and/or reduce oncogene expression has been identified as a promising cancer therapy. This study evaluated the selectivity and affinity of the silver^II complex of 5,10,15,20-tetrakis(<i>N</i>-methyl-4-pyridinium)porphyrin (<b>AgTMPyP</b>) to stabilize DNA sequences capable of forming G4 structures mimicking the telomeric and oncogene regions, using spectroscopic, biochemical methods and in vitro assays. The tetracationic silver complex was compared with the free base, <b>H₂TMPyP</b>, and the zinc^II complex, <b>ZnTMPyP</b>. The results obtained from UV-Vis and fluorescence methods pointed to a great affinity and good selectivity of <b>AgTMPyP</b> to G4 structures, especially for the oncogene <i>MYC.</i> In general, an increase in the ability of the studied ligands for ¹O₂ generation when interacting with oncogenic and telomeric G4 sequences was found. The results of the PCR stop assays proved that <b>AgTMPyP</b> has the ability to inhibit Taq polymerase. Additionally, in vitro assays demonstrated that the silver^II complex exhibits low cytotoxicity against HaCaT- an immortalized, non-tumorigenic, skin keratinocytes cell line-and, although nonexclusive, <b>AgTMPyP</b> shows nuclear co-localization.