title: Towards targeting anticancer drugs: ruthenium(ii)-arene complexes with biologically active naphthoquinone-derived ligand systems.
abstract: Anticancer active metal complexes with biologically active ligands have the potential to interact with more than one biological target, which could help to overcome acquired and/or intrinsic resistance of tumors to small molecule drugs. In this paper we present the preparation of 2-hydroxy-[1,4]-naphthoquinone-derived ligands and their coordination to a Ru(II)(η(6)-p-cymene)Cl moiety. The synthesis of oxime derivatives resulted in the surprising formation of nitroso-naphthalene complexes, as confirmed by X-ray diffraction analysis. The compounds were shown to be stable in aqueous solution but reacted with glutathione and ascorbic acid rather than undergoing reduction. One-electron reduction with pulse radiolysis revealed different behavior for the naphthoquinone and nitroso-naphthalene complexes, which was also observed in in vitro anticancer assays.
authors.affiliation: University of Auckland, School of Chemical Sciences, Private Bag 92019, Auckland 1142, New Zealand. c.hartinger@auckland.ac.nz.
authors.forename: Mario
authors.initials: M
authors.lastname: Kubanik
authors.affiliation: University of Vienna, Faculty of Chemistry, Institute of Inorganic Chemistry, Waehringer Str. 42, A-1090 Vienna, Austria and University of Vienna, Research Platform Translational Cancer Therapy Research, Waehringer Str. 42, A-1090 Vienna, Austria.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Kandioller
authors.affiliation: University of Auckland, School of Chemical Sciences, Private Bag 92019, Auckland 1142, New Zealand. c.hartinger@auckland.ac.nz.
authors.forename: Kunwoo
authors.initials: K
authors.lastname: Kim
authors.affiliation: University of Auckland, School of Chemical Sciences, Private Bag 92019, Auckland 1142, New Zealand. c.hartinger@auckland.ac.nz and Auckland Cancer Society Research Centre, Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, Auckland 1142, New Zealand.
authors.forename: Robert F
authors.initials: RF
authors.lastname: Anderson
authors.affiliation: University of Vienna, Faculty of Chemistry, Institute of Inorganic Chemistry, Waehringer Str. 42, A-1090 Vienna, Austria.
authors.forename: Erik
authors.initials: E
authors.lastname: Klapproth
authors.affiliation: University of Vienna, Faculty of Chemistry, Institute of Inorganic Chemistry, Waehringer Str. 42, A-1090 Vienna, Austria and University of Vienna, Research Platform Translational Cancer Therapy Research, Waehringer Str. 42, A-1090 Vienna, Austria.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Jakupec
authors.affiliation: University of Vienna, Faculty of Chemistry, Institute of Inorganic Chemistry, Waehringer Str. 42, A-1090 Vienna, Austria and University of Vienna, Research Platform Translational Cancer Therapy Research, Waehringer Str. 42, A-1090 Vienna, Austria.
authors.forename: Alexander
authors.initials: A
authors.lastname: Roller
authors.affiliation: University of Auckland, School of Chemical Sciences, Private Bag 92019, Auckland 1142, New Zealand. c.hartinger@auckland.ac.nz.
authors.forename: Tilo
authors.initials: T
authors.lastname: Söhnel
authors.affiliation: University of Vienna, Faculty of Chemistry, Institute of Inorganic Chemistry, Waehringer Str. 42, A-1090 Vienna, Austria and University of Vienna, Research Platform Translational Cancer Therapy Research, Waehringer Str. 42, A-1090 Vienna, Austria.
authors.forename: Bernhard K
authors.initials: BK
authors.lastname: Keppler
authors.affiliation: University of Auckland, School of Chemical Sciences, Private Bag 92019, Auckland 1142, New Zealand. c.hartinger@auckland.ac.nz and University of Vienna, Faculty of Chemistry, Institute of Inorganic Chemistry, Waehringer Str. 42, A-1090 Vienna, Austria and University of Vienna, Research Platform Translational Cancer Therapy Research, Waehringer Str. 42, A-1090 Vienna, Austria.
authors.forename: Christian G
authors.initials: CG
authors.lastname: Hartinger
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D001205:Ascorbic Acid / Q000737:chemistry; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D056831:Coordination Complexes / Q000737:chemistry* / Q000494:pharmacology; D000081007:Cymenes; D019008:Drug Resistance, Neoplasm; D005978:Glutathione / Q000737:chemistry; D006801:Humans; D039821:Monoterpenes / Q000737:chemistry* / Q000494:pharmacology; D009285:Naphthoquinones / Q000737:chemistry* / Q000494:pharmacology; D012428:Ruthenium / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D000081007:Cymenes; D039821:Monoterpenes; D009285:Naphthoquinones; C007210:4-cymene; D012428:Ruthenium; D005978:Glutathione; D001205:Ascorbic Acid