title: Studies on characterization, telomerase inhibitory properties and G-quadruplex binding of η6-arene ruthenium complexes with 1,10-phenanthroline-derived ligands.
abstract: Two arene ruthenium complexes [Ru(η(6)-C(6)H(6))(p-MOPIP)Cl](+)1 and [Ru(η(6)-C(6)H(6))(p-CFPIP)Cl](+)2, where p-MOPIP = 2-(4-methoxyphenyl)-imidazo[4,5f][1,10] phenanthroline and p-CFPIP = 2-(4-trifluoromethylphenyl)-imidazo[4,5f][1,10] phenanthroline, were prepared and the interactions of these compounds with DNA oligomers 5'-G3(T2AG3)3-3'(HTG21) have been studied by UV-vis and circular dichroism (CD) spectroscopy, gel mobility shift assay, fluorescence resonance energy transfer (FRET) melting assay, polymerase chain reaction (PCR) stop assay and telomeric repeat amplification protocol (TRAP) assay. The results show that both complexes can induce the stabilization of quadruplex DNA but complex 1 is a better G-quadruplex binder than complex 2. The two ruthenium complexes tested led to an inhibition of the enzyme telomerase and complex 1 was the significantly better inhibitor. A novel visual method has been developed for making a distinction between G-quadruplex DNA and double DNA by our Ru complexes binding hemin to form the hemin-G-quadruplex DNAzyme. Furthermore, in vitro cytotoxicity studies showed complex 1 exhibited quite potent antitumor activities and the greatest inhibitory selectivity against cancer cell lines.
authors.affiliation: Department of Chemistry, Jinan University, Guangzhou, 510632, PR China.
authors.forename: Dongdong
authors.initials: D
authors.lastname: Sun
authors.forename: Rong
authors.initials: R
authors.lastname: Zhang
authors.forename: Fang
authors.initials: F
authors.lastname: Yuan
authors.forename: Du
authors.initials: D
authors.lastname: Liu
authors.forename: Yanhui
authors.initials: Y
authors.lastname: Zhou
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
mesh_terms: D000818:Animals; D002417:Cattle; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D056831:Coordination Complexes / Q000737:chemistry* / Q000494:pharmacology; D004247:DNA / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D054856:G-Quadruplexes / Q000187:drug effects*; D006801:Humans; D008024:Ligands; D010618:Phenanthrolines / Q000737:chemistry* / Q000494:pharmacology; D012428:Ruthenium / Q000737:chemistry* / Q000494:pharmacology; D019098:Telomerase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013816:Thermodynamics
chemical_list: D056831:Coordination Complexes; D004791:Enzyme Inhibitors; D008024:Ligands; D010618:Phenanthrolines; D012428:Ruthenium; D004247:DNA; C427203:calf thymus DNA; D019098:Telomerase; C025205:1,10-phenanthroline