Dicopper(II) and Dizinc(II) Complexes with Nonsymmetric Dinucleating Ligands Based on Indolo[3,2-c]quinolines: Synthesis, Structure, Cytotoxicity, and Intracellular Distribution

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• 作者：Michael F. Primik ; Simone G枚schl ; Samuel M. Meier ; Nadine Eberherr ; Michael A. Jakupec ; 脡va A. Enyedy ; Ghenadie Novitchi ; Vladimir B. Arion
• 刊名：Inorganic Chemistry
• 出版年：2013
• 出版时间：September 3, 2013
• 年：2013
• 卷：52
• 期：17
• 页码：10137-10146
• 全文大小：490K
• 年卷期：v.52,no.17(September 3, 2013)
• ISSN：1520-510X

文摘

Dicopper(II) and dizinc(II) complexes [Cu₂(^MeOOCL^COO)(CH₃COO)₂] (1) and [Zn₂(^MeOOCL^COO)(CH₃COO)₂] (2) were synthesized by reaction of Cu(CH₃COO)₂路H₂O and Zn(CH₃COO)₂路2H₂O with a new nonsymmetric dinucleating ligand ^EtOOCHL^COOEt prepared by condensation of 6-hydrazinyl-11H-indolo[3,2-c]quinoline with diethyl-2,2鈥?((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鈥搗is, ¹H and ¹³C NMR spectroscopy), ESI mass spectrometry, magnetic susceptibility measurements, and UV鈥搗is complex formation studies (for 1) as well as by X-ray crystallography (1 and 2). The antiproliferative activity of ^EtOOCHL^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 ^EtOOCHL^COOEt is also discussed. The subcellular distribution of ^EtOOCHL^COOEt and 2 was investigated by fluorescence microscopy, revealing similar localization for both compounds in cytoplasmic structures.