Metal centers and aromatic moieties in Schiff base complexes: impact on G-quadruplex stabilization and oncogene downregulation

Abstract

We present the synthesis and characterization of novel square planar transition metal complexes of Schiff base ligands, which act as guanine quadruplex binders and stabilizers. The complexes stabilize quadruplexes related to telomere stability or present in oncogene regulatory sequences, as determined by optical spectroscopy, pointing out the emergence of selectivity towards specific structures or sequences. These results are supported and rationalized by molecular modeling simulations. Furthermore, we show that the treatment of cancer cell lines with our complexes is associated with the increase in the number of nuclear guanine quadruplexes and the downregulation in the expression of the considered oncogenes. Remarkably, only very moderate cytotoxicity can be observed for all complexes. These results pave the way for the development of selective anticancer treatment by metal compounds targeting the expression of specific oncogenes.