title: Cytotoxicity and preliminary mode of action studies of novel 2-aryl-4-thiopyrone-based organometallics.
abstract: Organometallic complexes with thiopyrone-based ligands have shown promising cytotoxic activity in vitro. To investigate the impact of the ligand backbone modification of these biologically active compounds and enhance the solubility in aqueous solution, the (thio)pyrone scaffold was modified via Suzuki-Miyaura coupling reaction and converted into corresponding organometallic Ru(ii) and Rh(iii) complexes. Characterization of the synthesized compounds was carried out by means of 1D and 2D NMR, ESI MS, and also by X-ray diffraction analysis. The stability in aqueous solution was investigated via(1)H NMR spectroscopy. Due to the close structural resemblance to flavonoids, topoisomerase inhibition, the cytotoxicity in human cancer cell lines as well as ROS generation was investigated by means of the topoisomerase II drug screening assay, the MTT assay and DCFH-DA assay, respectively.
authors.affiliation: Institute of Inorganic Chemistry, Faculty of Chemistry, University of Vienna, Waehringer Str. 42, A-1090 Vienna, Austria.
authors.forename: Melanie
authors.initials: M
authors.lastname: Schmidlehner
authors.affiliation: Institute of Inorganic Chemistry, Faculty of Chemistry, University of Vienna, Waehringer Str. 42, A-1090 Vienna, Austria.
authors.forename: Lea S
authors.initials: LS
authors.lastname: Flocke
authors.affiliation: Institute of Inorganic Chemistry, Faculty of Chemistry, University of Vienna, Waehringer Str. 42, A-1090 Vienna, Austria.
authors.forename: Alexander
authors.initials: A
authors.lastname: Roller
authors.affiliation: Institute of Inorganic Chemistry, Faculty of Chemistry, University of Vienna, Waehringer Str. 42, A-1090 Vienna, Austria.
authors.forename: Michaela
authors.initials: M
authors.lastname: Hejl
authors.affiliation: Institute of Inorganic Chemistry, Faculty of Chemistry, University of Vienna, Waehringer Str. 42, A-1090 Vienna, Austria and University of Vienna, Research Platform "Translational Cancer Therapy Research", Waehringer Str. 42, A-1090 Vienna, Austria. wolfgang.kandioller@univie.ac.at.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Jakupec
authors.affiliation: Institute of Inorganic Chemistry, Faculty of Chemistry, University of Vienna, Waehringer Str. 42, A-1090 Vienna, Austria and University of Vienna, Research Platform "Translational Cancer Therapy Research", Waehringer Str. 42, A-1090 Vienna, Austria. wolfgang.kandioller@univie.ac.at.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Kandioller
authors.affiliation: Institute of Inorganic Chemistry, Faculty of Chemistry, University of Vienna, Waehringer Str. 42, A-1090 Vienna, Austria and University of Vienna, Research Platform "Translational Cancer Therapy Research", Waehringer Str. 42, A-1090 Vienna, Austria. wolfgang.kandioller@univie.ac.at.
authors.forename: Bernhard K
authors.initials: BK
authors.lastname: Keppler
mesh_terms: D000951:Antigens, Neoplasm / Q000378:metabolism; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D018360:Crystallography, X-Ray; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008024:Ligands; D008968:Molecular Conformation; D009942:Organometallic Compounds / Q000737:chemistry*; D011753:Pyrones / Q000737:chemistry*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012428:Ruthenium / Q000737:chemistry; D012995:Solubility; D013329:Structure-Activity Relationship
chemical_list: D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D056831:Coordination Complexes; D004268:DNA-Binding Proteins; D008024:Ligands; D009942:Organometallic Compounds; D011753:Pyrones; D017382:Reactive Oxygen Species; D012428:Ruthenium; D004250:DNA Topoisomerases, Type II