title: The first metal-based paullone derivative with high antiproliferative activity in vitro.
abstract: 9-Bromo-7,12-dihydroindolo[3,2-d][1]benzazepin-6(5H)-one, kenpaullone, which displays similarities in the activity profile to flavopiridol, was modified by chemical transformations at the lactam unit to provide a peripheral binding site able to accommodate metal ions. The first metal-based paullone has been prepared and characterized by single-crystal X-ray diffraction methods, solid-state cross-polarization magic angle spinning 13C NMR spectroscopy, electrospray ionization mass spectra, and electronic spectra. The gallium complex [GaL2]Cl.2.5H2O, the metal-free ligand (HL), and the starting compound used for the preparation of HL were assessed in vitro for their cytotoxicity in a panel of human tumor cell lines. The gallium complex was found to be 1.5-18-fold more cytotoxic than HL, with an average IC50 value of 2.0 microM.
authors.affiliation: Institute of Inorganic Chemistry, University of Vienna, Waehringerstrasse 42, A-1090 Vienna, Austria.
authors.forename: Anatoly
authors.initials: A
authors.lastname: Dobrov
authors.forename: Vladimir B
authors.initials: VB
authors.lastname: Arion
authors.forename: Norbert
authors.initials: N
authors.lastname: Kandler
authors.forename: Werner
authors.initials: W
authors.lastname: Ginzinger
authors.forename: Michael A
authors.initials: MA
authors.lastname: Jakupec
authors.forename: Anna
authors.initials: A
authors.lastname: Rufińska
authors.forename: Nikolai
authors.initials: N
authors.lastname: Graf von Keyserlingk
authors.forename: Mathea Sophia
authors.initials: MS
authors.lastname: Galanski
authors.forename: Christian
authors.initials: C
authors.lastname: Kowol
authors.forename: Bernhard K
authors.initials: BK
authors.lastname: Keppler
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D004354:Drug Screening Assays, Antitumor; D005419:Flavonoids / Q000737:chemistry; D032061:Galium / Q000737:chemistry; D006801:Humans; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008670:Metals / Q000737:chemistry; D015394:Molecular Structure; D010880:Piperidines / Q000737:chemistry; D021241:Spectrometry, Mass, Electrospray Ionization; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D005419:Flavonoids; D008024:Ligands; D008670:Metals; D010880:Piperidines; C077990:alvocidib