title: Dicopper(II) and dizinc(II) complexes with nonsymmetric dinucleating ligands based on indolo[3,2-c]quinolines: synthesis, structure, cytotoxicity, and intracellular distribution.
abstract: Dicopper(II) and dizinc(II) complexes [Cu2((MeOOC)L(COO))(CH3COO)2] (1) and [Zn2((MeOOC)L(COO))(CH3COO)2] (2) were synthesized by reaction of Cu(CH3COO)2·H2O and Zn(CH3COO)2·2H2O with a new nonsymmetric dinucleating ligand (EtOOC)HL(COOEt) prepared by condensation of 6-hydrazinyl-11H-indolo[3,2-c]quinoline with diethyl-2,2'-((3-formyl-2-hydroxy-5-methylbenzyl)azanediyl)diacetate. The design and synthesis of this elaborate ligand was performed with the aim of increasing the aqueous solubility of indolo[3,2-c]quinolines, known as biologically active compounds, and investigating the antiproliferative activity in human cancer cell lines and the cellular distribution by exploring the intrinsic fluorescence of the indoloquinoline scaffold. The compounds have been comprehensively characterized by elemental analysis, spectroscopic methods (IR, UV-vis, (1)H and (13)C NMR spectroscopy), ESI mass spectrometry, magnetic susceptibility measurements, and UV-vis complex formation studies (for 1) as well as by X-ray crystallography (1 and 2). The antiproliferative activity of (EtOOC)HL(COOEt), 1, and 2 was determined by the MTT assay in three human cancer cell lines, namely, A549 (nonsmall cell lung carcinoma), CH1 (ovarian carcinoma), and SW480 (colon adenocarcinoma), yielding IC50 values in the micromolar concentration range and showing dependence on the cell line. The effect of metal coordination on cytotoxicity of (EtOOC)HL(COOEt) is also discussed. The subcellular distribution of (EtOOC)HL(COOEt) and 2 was investigated by fluorescence microscopy, revealing similar localization for both compounds in cytoplasmic structures.
authors: Institute of Inorganic Chemistry, University of Vienna, Währinger Strasse 42, A-1090 Vienna, Austria.
authors: Michael F
authors: MF
authors: Primik
authors: Simone
authors: S
authors: Göschl
authors: Samuel M
authors: SM
authors: Meier
authors: Nadine
authors: N
authors: Eberherr
authors: Michael A
authors: MA
authors: Jakupec
authors: Éva  A
authors: É
authors: Enyedy
authors: Ghenadie
authors: G
authors: Novitchi
authors: Vladimir B
authors: VB
authors: Arion
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D003300:Copper / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D018360:Crystallography, X-Ray; D006801:Humans; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D009369:Neoplasms / Q000188:drug therapy; D011804:Quinolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D021241:Spectrometry, Mass, Electrospray Ionization; D015032:Zinc / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D008024:Ligands; D011804:Quinolines; D003300:Copper; D015032:Zinc
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