title: Synthesis, structures, cellular uptake and apoptosis-inducing properties of highly cytotoxic ruthenium-Norharman complexes.
abstract: Three novel Ru(II) complexes of the general formula [Ru(N-N)(2)(Norharman)(2)](SO(3)CF(3))(2), where N-N = 2,2'-bipyridine (bpy, 1), 1,10-phenanthroline (phen, 2), 4,7-diphenyl-1,10-phenanthroline (DIP, 3) and Norharman (9H-pyrido[3,4-b]indole) is a naturally occurring β-carboline alkaloid, have been synthesized and characterized. The molecular structures of 1 and 2 have been determined by X-ray diffraction analysis. The cellular uptake efficiencies, in vitro cytotoxicities and apoptosis-inducing properties of these complexes have been extensively explored. Notably, 1-3 exhibit potent antiproliferative activities against a panel of human cancer cell lines with IC(50) values lower than those of cisplatin. Further studies show that 1-3 can cause cell cycle arrest in the G0/G1 phase and induce apoptosis through mitochondrial dysfunction and reactive oxygen species (ROS) generation. In vitro DNA binding studies have also been conducted to provide information about the possible mechanism of action.
authors.affiliation: State Key Laboratory of Biocontrol, Department of Biochemistry, College of Life Sciences, Sun Yat-sen University, Guangzhou, 510006, PR China.
authors.forename: Caiping
authors.initials: C
authors.lastname: Tan
authors.forename: Shouhai
authors.initials: S
authors.lastname: Wu
authors.forename: Sensen
authors.initials: S
authors.lastname: Lai
authors.forename: Minxu
authors.initials: M
authors.lastname: Wang
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.forename: Lingjun
authors.initials: L
authors.lastname: Zhou
authors.forename: Yiping
authors.initials: Y
authors.lastname: Zhu
authors.forename: Wu
authors.initials: W
authors.lastname: Lian
authors.forename: Wenlie
authors.initials: W
authors.lastname: Peng
authors.forename: Liangnian
authors.initials: L
authors.lastname: Ji
authors.forename: Anlong
authors.initials: A
authors.lastname: Xu
mesh_terms: D000470:Alkaloids / Q000138:chemical synthesis / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis; D017209:Apoptosis / Q000187:drug effects*; D001688:Biological Products / Q000138:chemical synthesis / Q000494:pharmacology; D002243:Carbolines; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D003603:Cytotoxins / Q000138:chemical synthesis*; D004247:DNA / Q000378:metabolism; D006247:Harmine / Q000031:analogs & derivatives* / Q000737:chemistry; D006801:Humans; D020128:Inhibitory Concentration 50; D008928:Mitochondria / Q000187:drug effects; D009942:Organometallic Compounds / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity*; D010599:Pharmacokinetics; D017382:Reactive Oxygen Species; D012428:Ruthenium / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity*; D014961:X-Ray Diffraction
chemical_list: D000470:Alkaloids; D000970:Antineoplastic Agents; D001688:Biological Products; D002243:Carbolines; D003603:Cytotoxins; D009942:Organometallic Compounds; D017382:Reactive Oxygen Species; D006247:Harmine; D012428:Ruthenium; D004247:DNA; C010262:norharman