Syntheses of polypyridyl metal complexes and studies of their interaction with quadruplex DNA.

A series of mono- and bi-metallic metal complexes (with Cu(II), Pt(II) and Zn(II)) with substituted polypyridyl ligands have been prepared and their binding affinities towards quadruplex (c-Myc and human telomeric) and duplex DNA (ds26 and calf thymus) determined using fluorescent indicator displacement (FID) assays and UV/vis spectroscopic titrations. These studies have shown that the number of aromatic rings and number/position of cyclic amine substituents on the ligands, play an important role in defining the DNA binding abilities of the resulting metal complexes. We also show that bi-metallic complexes prepared using a novel terpyridine-cyclen ligand have higher affinity towards G-quadruplex DNA as compared to their mono-metallic counterparts.

Inhibition of mitogen-activated protein kinase (MAPK) and cyclin-dependent kinase 2 (Cdk2) by platinum(II) phenanthroline complexes.

Unlabelled: Inhibition of protein kinases in the fight against disease remains a constant challenge for medicinal chemists, who have screened multitudes of predominantly planar organic scaffolds, natural and synthetic, to identify potent-albeit not always selective-kinase inhibitors. Herein, in an effort to investigate the potential biological utility of metal-based compounds as inhibitors against the cancer-relevant targets mitogen-activated protein kinase and cyclin-dependent kinase 2, we explore various parameters in planar platinum(II) complexes with substituted phenanthroline ligands and aliphatic diamine chelate co-ligands, to identify combinations that yield promising inhibitory activity. The individual ligands' steric requirements as well as their pattern of hydrogen bond donors/acceptors appear to alter inhibitory potency when modulated.