title: Topoisomerase IIα poisoning and DNA double-strand breaking by chiral ruthenium(ii) complexes containing 2-furanyl-imidazo[4,5-f][1,10]phenanthroline derivatives.
abstract: Four chiral Ru(ii) complexes bearing furan ligands, Δ/Λ-[Ru(bpy)2(pocl)](2+) () and Δ/Λ-[Ru(bpy)2(poi)](2+) () (bpy = 2,2'-bipyridine, pocl = 2-(5-chlorofuran-2-yl)imidazo[4,5-f][1,10]phenanthroline, poi = 2-(5-5-iodofuran-2-yl)imidazo[4,5-f][1,10]phenanthroline), were synthesized and characterized. These Ru(ii) complexes showed antitumor activities against HeLa, A549, HepG2, HL-60 and K562 tumor cell lines, especially the HL-60 tumor cell line. Moreover, was more active than other complexes accounting for the different cellular uptakes. In addition, could accumulate in the nucleus of HL-60 cells, suggesting that nucleic acids were the cellular target of . Topoisomerase inhibition tests in vitro and in living cells confirmed that the four complexes acted as efficient topoisomerase IIα poisons, DNA double-strand breaks had also been observed from neutral single cell gel electrophoresis (comet assay). inhibited the growth of HL-60 cells through the induction of apoptotic cell death, as evidenced by the Alexa Fluor® 488 annexin V staining assays. The results demonstrated that acted as a topoisomerase IIα poison and caused DNA double-strand damage that could lead to apoptosis.
authors.affiliation: MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou, 510275, P. R. China. cesjln@mail.sysu.edu.cn ceschh@mail.sysu.edu.cn.
authors.forename: Chen
authors.initials: C
authors.lastname: Qian
authors.affiliation: MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou, 510275, P. R. China. cesjln@mail.sysu.edu.cn ceschh@mail.sysu.edu.cn.
authors.forename: Jingheng
authors.initials: J
authors.lastname: Wu
authors.affiliation: MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou, 510275, P. R. China. cesjln@mail.sysu.edu.cn ceschh@mail.sysu.edu.cn.
authors.forename: Liangnian
authors.initials: L
authors.lastname: Ji
authors.affiliation: MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou, 510275, P. R. China. cesjln@mail.sysu.edu.cn ceschh@mail.sysu.edu.cn.
authors.forename: Hui
authors.initials: H
authors.lastname: Chao
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D056831:Coordination Complexes / Q000737:chemistry / Q000494:pharmacology*; D053903:DNA Breaks, Double-Stranded / Q000187:drug effects*; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D006801:Humans; D062105:Molecular Docking Simulation; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D010618:Phenanthrolines / Q000737:chemistry / Q000494:pharmacology*; D012428:Ruthenium / Q000737:chemistry / Q000494:pharmacology*; D059005:Topoisomerase II Inhibitors / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D010618:Phenanthrolines; D059005:Topoisomerase II Inhibitors; D012428:Ruthenium; D004250:DNA Topoisomerases, Type II