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(MeOOCLCOO)(CH3COO)2] (1) and [Zn2(MeOOCLCOO)(CH3COO)2] (2) were synthesized by reaction of Cu(CH3COO)2·H2O and Zn(CH3COO)2·2H2O with a new nonsymmetric dinucleating ligand EtOOCHLCOOEt 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, 1H and 13C 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 EtOOCHLCOOEt, 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 EtOOCHLCOOEt is also discussed. The subcellular distribution of EtOOCHLCOOEt and 2 was investigated by fluorescence microscopy, revealing similar localization for both compounds in cytoplasmic structures.