Platinum(II) complexes with dipyridophenazine ligands as human telomerase inhibitors and luminescent probes for G-quadruplex DNA.
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.
Ma
Dik-Lung
DL
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.
Che
Chi-Ming
CM
Yan
Siu-Cheong
SC
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
D004791:Enzyme Inhibitors; D008024:Ligands; D009944:Organoplatinum Compounds; D010619:Phenazines; D011725:Pyridines; D059004:Topoisomerase I Inhibitors; C058324:2-phenylpyridine; D004247:DNA