title: Platinum(II) complexes with dipyridophenazine ligands as human telomerase inhibitors and luminescent probes for G-quadruplex DNA.
abstract: A series of platinum(II) complexes containing dipyridophenazine (dppz) and C-deprotonated 2-phenylpyridine (N-CH) ligands were prepared and assayed for G-quadruplex DNA binding activities. [PtII(dppz-COOH)(N-C)]CF3SO3 (1; dppz-COOH = 11-carboxydipyrido[3,2-a:2',3'-c]phenazine) binds G-quadruplex DNA through an external end-stacking mode with a binding affinity of approximately 10(7) dm3 mol-1. G-quadruplex DNA binding is accompanied by up to a 293-fold increase in the intensity of photoluminescence at lambdamax = 512 nm. Using a biotinylated-primer extension telomerase assay, 1 was shown to be an effective inhibitor of human telomerase in vitro, with a telIC50 value of 760 nM.
authors.affiliation: Department of Chemistry and Open Laboratory of Chemical Biology of the Institute of Molecular Technology for Drug Discovery and Synthesis, The University of Hong Kong, Pokfulam Road, Hong Kong.
authors.forename: Dik-Lung
authors.initials: DL
authors.lastname: Ma
authors.forename: Chi-Ming
authors.initials: CM
authors.lastname: Che
authors.forename: Siu-Cheong
authors.initials: SC
authors.lastname: Yan
mesh_terms: D002460:Cell Line; D004247:DNA / Q000032:analysis* / Q000737:chemistry; D004591:Electrophoresis, Polyacrylamide Gel; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D054856:G-Quadruplexes; D006367:HeLa Cells; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D009944:Organoplatinum Compounds / Q000737:chemistry* / Q000494:pharmacology; D010619:Phenazines / Q000737:chemistry; D011725:Pyridines / Q000737:chemistry; D013056:Spectrophotometry, Ultraviolet; D017186:Titrimetry; D059004:Topoisomerase I Inhibitors
chemical_list: D004791:Enzyme Inhibitors; D008024:Ligands; D009944:Organoplatinum Compounds; D010619:Phenazines; D011725:Pyridines; D059004:Topoisomerase I Inhibitors; C058324:2-phenylpyridine; D004247:DNA