title: Gallium(III) and iron(III) complexes of alpha-N-heterocyclic thiosemicarbazones: synthesis, characterization, cytotoxicity, and interaction with ribonucleotide reductase.
abstract: A series of gallium(III) and iron(III) complexes with five different 4N-substituted alpha-N-heterocyclic thiosemicarbazones, viz., 2-acetylpyridine N,N-dimethylthiosemicarbazone (1), 2-acetylpyridine N-pyrrolidinylthiosemicarbazone (2), acetylpyrazine N,N-dimethylthiosemicarbazone (3), acetylpyrazine N-pyrrolidinylthiosemicarbazone (4), and acetylpyrazine N-piperidinylthiosemicarbazone (5), with the general formula [GaLCl2] (HL = 1 and 2) and [ML2][Y] (M = Ga, HL = 1-5, Y = PF6; M = Fe, HL = 1-5, Y = FeCl4 and PF6) were synthesized and characterized by elemental analysis, a number of spectroscopic methods (NMR, IR, UV-vis), mass spectrometry, and X-ray crystallography. The in vitro antitumor potency was studied in two human cancer cell lines (41M and SK-BR-3). The central metal ions exert pronounced effects in a divergent manner: gallium(III) enhances, whereas iron(III) weakens the cytotoxicity of the ligands. The capacity of ligand 1 and its Ga(III) and Fe(III) complexes to destroy the tyrosyl radical of the presumed target ribonucleotide reductase is reported.
authors.affiliation: Institute of Inorganic Chemistry, Faculty of Chemistry, University of Vienna, Waehringer Strasse 42, A-1090 Vienna, Austria.
authors.forename: Christian R
authors.initials: CR
authors.lastname: Kowol
authors.forename: Roland
authors.initials: R
authors.lastname: Berger
authors.forename: Rene
authors.initials: R
authors.lastname: Eichinger
authors.forename: Alexander
authors.initials: A
authors.lastname: Roller
authors.forename: Michael A
authors.initials: MA
authors.lastname: Jakupec
authors.forename: Peter P
authors.initials: PP
authors.lastname: Schmidt
authors.forename: Vladimir B
authors.initials: VB
authors.lastname: Arion
authors.forename: Bernhard K
authors.initials: BK
authors.lastname: Keppler
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D002614:Chelating Agents / Q000138:chemical synthesis* / Q000737:chemistry; D018360:Crystallography, X-Ray; D004354:Drug Screening Assays, Antitumor; D005609:Free Radicals / Q000737:chemistry; D005708:Gallium; D006801:Humans; D007501:Iron; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D051379:Mice; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D012264:Ribonucleotide Reductases / Q000737:chemistry*; D013055:Spectrophotometry, Infrared; D013056:Spectrophotometry, Ultraviolet; D013329:Structure-Activity Relationship; D013882:Thiosemicarbazones / Q000138:chemical synthesis* / Q000737:chemistry; D014443:Tyrosine / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D002614:Chelating Agents; D005609:Free Radicals; D008024:Ligands; D009942:Organometallic Compounds; D013882:Thiosemicarbazones; D014443:Tyrosine; D005708:Gallium; D007501:Iron; D012264:Ribonucleotide Reductases; C108427:ribonucleotide reductase R2 subunit