title: Anticancer activity of Ru- and Os(arene) compounds of a maleimide-functionalized bioactive pyridinecarbothioamide ligand.
abstract: With the aim of increasing the accumulation of Ru anticancer agents in the tumor, a targeted delivery strategy based on a maleimide anchor for the biological vector human serum albumin (HSA) was developed. A group of piano stool Ru- and Os(η6-arene) complexes carrying a maleimide-functionalized N-phenyl-2-pyridinecarbothioamide (PCA) ligand was designed allowing for covalent conjugation to biological thiols. The complexes were characterized by NMR spectroscopy, ESI-MS, elemental analysis and single-crystal X-ray diffraction analysis. The compounds were shown to undergo halido/aqua ligand exchange reactions in aqueous solution, depending mainly on the metal center and the nature of the halide. In vitro cytotoxicity studies revealed low potency which is explained by the observed high reactivity of the maleimide to the thiol of l-cysteine (Cys), while the metal center itself shows little affinity to amino acids of the model protein lysozyme.
authors.affiliation: School of Chemical Sciences, University of Auckland, Private Bag 92019, Auckland 1142, New Zealand.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Hanif
authors.affiliation: School of Chemical Sciences, University of Auckland, Private Bag 92019, Auckland 1142, New Zealand.
authors.forename: Sally
authors.initials: S
authors.lastname: Moon
authors.affiliation: School of Chemical Sciences, University of Auckland, Private Bag 92019, Auckland 1142, New Zealand; School of Biological Sciences, University of Auckland, Private Bag 92019, Auckland 1142, New Zealand.
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Sullivan
authors.affiliation: School of Chemical Sciences, University of Auckland, Private Bag 92019, Auckland 1142, New Zealand.
authors.forename: Sanam
authors.initials: S
authors.lastname: Movassaghi
authors.affiliation: School of Chemical Sciences, University of Auckland, Private Bag 92019, Auckland 1142, New Zealand.
authors.forename: Mario
authors.initials: M
authors.lastname: Kubanik
authors.affiliation: School of Biological Sciences, University of Auckland, Private Bag 92019, Auckland 1142, New Zealand.
authors.forename: David C
authors.initials: DC
authors.lastname: Goldstone
authors.affiliation: School of Chemical Sciences, University of Auckland, Private Bag 92019, Auckland 1142, New Zealand.
authors.forename: Tilo
authors.initials: T
authors.lastname: Söhnel
authors.affiliation: Auckland Cancer Society Research Centre, University of Auckland, Private Bag 92019, Auckland 1142, New Zealand.
authors.forename: Stephen M F
authors.initials: SM
authors.lastname: Jamieson
authors.affiliation: School of Chemical Sciences, University of Auckland, Private Bag 92019, Auckland 1142, New Zealand. Electronic address: c.hartinger@auckland.ac.nz.
authors.forename: Christian G
authors.initials: CG
authors.lastname: Hartinger
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D003603:Cytotoxins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D009992:Osmium; D012428:Ruthenium; D012709:Serum Albumin / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D003603:Cytotoxins; D009942:Organometallic Compounds; D012709:Serum Albumin; D009992:Osmium; D012428:Ruthenium
keywords: Albumin carrier; Anticancer agents; Bioorganometallics; Maleimide; Ru(arene) complexes