title: Novel platinum complexes as efficient G-quadruplex DNA binders and telomerase inhibitors.
abstract: Three 4-(1H-imidazo[4,5-f]-1,10-phenanthrolin-2-yl)phenol derivatives-based platinum (II) complexes have been synthesized, and their G-quadruplex DNAs-binding interactions, telomerase inhibition, antiproliferative activity, and cell cycle arrest were studied. Three complexes show the preference for stabilizing h-telo, c-kit2, and c-myc G-quadruplexes in the presence of 10-fold excess of duplex DNA and the higher binding affinities to G-quadruplexes than to duplex. The complexes 1 and 3 present a high stabilization potential (ΔTm) for h-telo G-quadruplex and thus give a significant inhibition of telomerase activity at 2μM concentration, whereas the complex 2 displays higher antiproliferative activity against HeLa and HepG2 cancer cells by MTT assay with IC50 values of about 10(-5)M. The complexes 2 and 3 arrest both cells in the G0/G1 phase of cell cycle, whereas the complex 1 arrests the cell cycle in the S phase for HeLa cells and the G0/G1 phase for HepG2 cells.
authors: Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Institute of Molecular Science, Shanxi University, Taiyuan 030006, PR China. weichuny@sxu.edu.cn
authors: Chunying
authors: C
authors: Wei
authors: Ye
authors: Y
authors: Wen
authors: Junhong
authors: J
authors: Wang
mesh_terms: D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis / Q000737:chemistry*; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D054856:G-Quadruplexes; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D009691:Nucleic Acid Denaturation; D010984:Platinum / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D019098:Telomerase / Q000037:antagonists & inhibitors*; D044366:Transition Temperature
chemical_list: D004791:Enzyme Inhibitors; D010984:Platinum; D004247:DNA; D019098:Telomerase