title: Synthesis and cellular impact of diene-ruthenium(II) complexes: a new class of organoruthenium anticancer agents.
abstract: The cytostatic properties and cellular effects of novel diene-ruthenium(II) complexes of the types OC-6-13-[RuCl(2)(pp)(cod)] 1-5 (pp=2,2'-bipyridyl (bpy), phen=1,10-phenanthroline (phen), 5,6-dimethylphenanthroline (5,6-Me2phen), dipyrido[3,2-d:2',3'-f]quinoxaline (dpq), ethylenediamine (en)) and OC-6-24-[RuCl{(Me(2)N)(2)CS}(pp)(cod)](CF(3)SO(3)) 6-8 (pp=phen, 5,6-Me(2)phen, dpq) have been studied for the human cancer cell lines MCF-7 and HT-29 and for Jurkat leukemia cells. CD spectra indicate that 7 causes a massive distortion of the CT DNA B double helix toward the A form. Whereas the neutral complexes 1, 2 and 5 exhibit only modest antiproliferative activity toward MCF-7 and HT-29 cells, the monocationic complexes are significantly more active, in particular the DNA-distorting complex 7 with its IC(50) values of 0.73 and 0.42 μM, respectively. As established by online monitoring with a cell-based sensor chip, this potent 5,6-Me(2)phen complex invokes dose-dependent decreases in MCF-7 cellular respiration and extracellular acidification rates and causes a time-delayed decrease in the impedance of the cell layers, that can be ascribed to cell death. Treatment of Jurkat cells with 7 leads to high concentrations of reactive oxygen species and the induction of apoptosis. The pronounced dose-dependent inhibition of oxygen consumption by isolated mice mitochondria indicates the involvement of an intrinsic mitochondrial pathway in the programmed cell death process.
authors: Fakultät für Chemie und Biochemie, Ruhr-Universität Bochum, Bochum, Germany.
authors: Christine
authors: C
authors: Kasper
authors: Hamed
authors: H
authors: Alborzinia
authors: Suzan
authors: S
authors: Can
authors: Igor
authors: I
authors: Kitanovic
authors: Andreas
authors: A
authors: Meyer
authors: Yvonne
authors: Y
authors: Geldmacher
authors: Melanie
authors: M
authors: Oleszak
authors: Ingo
authors: I
authors: Ott
authors: Stefan
authors: S
authors: Wölfl
authors: William S
authors: WS
authors: Sheldrick
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019069:Cell Respiration / Q000187:drug effects; D004273:DNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D005110:Extracellular Space / Q000737:chemistry / Q000187:drug effects; D019073:HT29 Cells; D006801:Humans; D006838:Hydrocarbons / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D019169:Jurkat Cells; D009690:Nucleic Acid Conformation / Q000187:drug effects; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D010101:Oxygen Consumption / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D012428:Ruthenium / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D006838:Hydrocarbons; D009942:Organometallic Compounds; D017382:Reactive Oxygen Species; D012428:Ruthenium