title: Ruthenium(II) polypyridyl complexes as dual inhibitors of telomerase and topoisomerase.
abstract: One novel ruthenium polypyridyl complex, [Ru(bpy)2(icip)](2+) (1), and two previously reported ruthenium polypyridyl complexes, [Ru(bpy)2(pdppz)](2+) ()2 and [Ru(bpy)2(tactp)](2+) (3) (bpy = 2,2'-bipyridine, icip = 2-(indeno[2,1-b]chromen-6-yl)-1H-imidazo[4,5-f][1,10]phenanthroline, pdppz = phenanthro[4,5-abc]dipyrido[3,2-h:2',3'-j]phenazine, tactp = 4,5,9,18-tetraazachryseno[9,10-b]-triphenylene), have been synthesised. As expected, these complexes show inhibition towards telomerase by inducing and stabilising the G-quadruplex structure, and behave as topoisomerase I/II poisons at the same time. Additionally, the acute and chronic cytotoxicities of the complexes are considered. Furthermore, cell apoptosis experiments are used to briefly study the mechanism. Because studies involving multi-target inhibition towards topoisomerase and telomerase of Ru(II) complexes have not been reported previously, the present research may help to develop innovative chemical strategies and therapies.
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. ceschh@mail.sysu.edu.cn.
authors.forename: Guoliang
authors.initials: G
authors.lastname: Liao
authors.forename: Xiang
authors.initials: X
authors.lastname: Chen
authors.forename: Jingheng
authors.initials: J
authors.lastname: Wu
authors.forename: Chen
authors.initials: C
authors.lastname: Qian
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.forename: Liangnian
authors.initials: L
authors.lastname: Ji
authors.forename: Hui
authors.initials: H
authors.lastname: Chao
mesh_terms: D015082:2,2'-Dipyridyl / Q000737:chemistry; D017209:Apoptosis; D002453:Cell Cycle; D049109:Cell Proliferation; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry; D026942:DNA Topoisomerases / Q000737:chemistry*; D015195:Drug Design; D005434:Flow Cytometry; D031541:Fluorescence Resonance Energy Transfer; D054856:G-Quadruplexes; D006367:HeLa Cells; D006801:Humans; D008856:Microscopy, Fluorescence; D016133:Polymerase Chain Reaction; D017975:Ruthenium Compounds / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization; D019098:Telomerase / Q000037:antagonists & inhibitors* / Q000737:chemistry; D013696:Temperature; D013816:Thermodynamics; D059003:Topoisomerase Inhibitors / Q000737:chemistry*
chemical_list: D017975:Ruthenium Compounds; D059003:Topoisomerase Inhibitors; D015082:2,2'-Dipyridyl; D004247:DNA; D019098:Telomerase; D026942:DNA Topoisomerases