Conjugation of Organoruthenium(II) 3-(1H-Benzimidazol-2-yl)pyrazolo[3,4-b]pyridines and Indolo[3,2-d]benzazepines to Recombinant Human Serum Albumin: a Strategy To Enhance Cytotoxicity in Cancer Cells

Five organoruthenium complexes [RuCl(η6-arene)(L)]Cl with a modified arene ligand, namely, 4-formylphenoxyacetyl-η6-benzylamide, and L = 3-(1H-benzimidazol-2-yl)-1H-pyrazolo[3,4-b]pyridines or indolo[3,2-d]benzazepines were synthesized and conjugated to recombinant human serum albumin in order to improve their drug targeting and delivery to cancer cells, and a marked increase in cytotoxicity was observed

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

Dicopper­(II) and dizinc­(II) complexes [Cu₂(^MeOOCL^COO)­(CH₃COO)₂] (<b>1</b>) and [Zn₂(^MeOOCL^COO)­(CH₃COO)₂] (<b>2</b>) were synthesized by reaction of Cu­(CH₃COO)₂·H₂O and Zn­(CH₃COO)₂·2H₂O with a new nonsymmetric dinucleating ligand ^<b>EtOOC</b><b>HL</b>^<b>COOEt</b> prepared by condensation of 6-hydrazinyl-11<i>H</i>-indolo­[3,2-<i>c</i>]­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-<i>c</i>]­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 <b>1</b>) as well as by X-ray crystallography (<b>1</b> and <b>2</b>). The antiproliferative activity of ^<b>EtOOC</b><b>HL</b>^<b>COOEt</b>, <b>1</b>, and <b>2</b> 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 ^<b>EtOOC</b><b>HL</b>^<b>COOEt</b> is also discussed. The subcellular distribution of ^<b>EtOOC</b><b>HL</b>^<b>COOEt</b> and <b>2</b> was investigated by fluorescence microscopy, revealing similar localization for both compounds in cytoplasmic structures