title: Syntheses of polypyridyl metal complexes and studies of their interaction with quadruplex DNA.
abstract: 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. Cytotoxicity assays were carried out for all the new complexes against an osteosarcoma cancer cell line (U2OS) as well as a normal fibroblast cell line (GM05757). Several of these compounds displayed cytotoxicity similar to that of cisplatin.
authors.affiliation: Department of Chemistry, Imperial College London, London SW7 2AZ, UK. r.vilar@imperial.ac.uk.
authors.forename: Verity S
authors.initials: VS
authors.lastname: Stafford
authors.forename: Kogularamanan
authors.initials: K
authors.lastname: Suntharalingam
authors.forename: Arun
authors.initials: A
authors.lastname: Shivalingam
authors.forename: Andrew J P
authors.initials: AJ
authors.lastname: White
authors.forename: David J
authors.initials: DJ
authors.lastname: Mann
authors.forename: Ramon
authors.initials: R
authors.lastname: Vilar
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D056831:Coordination Complexes / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D003300:Copper / Q000737:chemistry*; D018360:Crystallography, X-Ray; D000080027:Cyclams; D003603:Cytotoxins / Q000633:toxicity; D054856:G-Quadruplexes; D006571:Heterocyclic Compounds / Q000737:chemistry; D006801:Humans; D008024:Ligands; D008968:Molecular Conformation; D010984:Platinum / Q000737:chemistry*; D011725:Pyridines / Q000737:chemistry; D015032:Zinc / Q000737:chemistry*
chemical_list: D056831:Coordination Complexes; D000080027:Cyclams; D003603:Cytotoxins; D006571:Heterocyclic Compounds; D008024:Ligands; D011725:Pyridines; D010984:Platinum; D003300:Copper; C038072:cyclen; D015032:Zinc