Octahedral copper(ii)-diimine complexes of triethylenetetramine: effect of stereochemical fluxionality and ligand hydrophobicity on Cu
| Autor: | Mitu, Sharma, Mani, Ganeshpandian, Munmi, Majumder, Ajaykamal, Tamilarasan, Mukesh, Sharma, Rupak, Mukhopadhyay, Nashreen S, Islam, Mallayan, Palaniandavar |
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| Rok vydání: | 2020 |
| Předmět: |
Dose-Response Relationship
Drug Molecular Structure Antineoplastic Agents Apoptosis DNA Neoplasm Ligands Trientine Structure-Activity Relationship A549 Cells Coordination Complexes MCF-7 Cells Tumor Cells Cultured Humans Imines DNA Cleavage Drug Screening Assays Antitumor Reactive Oxygen Species Hydrophobic and Hydrophilic Interactions Oxidation-Reduction Copper Cell Proliferation |
| Zdroj: | Dalton transactions (Cambridge, England : 2003). 49(24) |
| ISSN: | 1477-9234 |
| Popis: | Octahedral copper(ii) complexes of the type [Cu(trien)(diimine)](ClO4)2 (1-4), where trien is triethylenetetramine and diimine is 2,2'-bipyridine (1), 1,10-phenanthroline (2), 5,6-dimethyl-1,10-phenanthroline (3), and 3,4,7,8-tetramethyl-1,10-phenanthroline (4), have been isolated. Single crystal X-ray structures of 1 and 2 reveal that the coordination geometry around Cu(ii) is tetragonally distorted octahedral. The stereochemical fluxionality of the complexes illustrates the observed trend in CuII/CuI redox potentials and DNA binding affinity (Kb: 1, 0.030 ± 0.0022, 0.66 ± 0.013, 1.63 ± 0.104, 2.27± 0.20 × 105 M-1), determined using absorption spectral titration. All complexes effect oxidative DNA cleavage more efficiently than hydrolytic DNA cleavage. The bpy complex 1 with stereochemical fluxionality lower than its phen analogue 2 shows a higher cytotoxicity against both A549 lung (IC50, 3.3 μM) and MCF-7 human breast (IC50, 3.9 μM) cancer cells, and induces the generation of the highest amount of ROS in A549 cells. Complex 3 with a higher stereochemical fluxionality and higher ligand hydrophobicity exhibits a higher DNA binding and cleavage ability and higher cytotoxicity (IC50, 2.1 μM) towards MCF-7 cells. Complex 4 with a still higher stereochemical fluxionality displays the highest DNA binding and cleavage ability but a lower cytotoxicity towards both A549 and MCF-7 cell lines due to its tendency to form a five-coordinated complex with the uncoordinated amine group. Annexin V.Cy3 staining and immunoblot analysis demonstrate the mechanism of cell death caused by 1 and 2. The finding of the up-regulation of the pro-apoptotic Bax protein and down-regulation of PARP protein in western blot analysis confirms the induction of apoptosis by these complexes. |
| Databáze: | OpenAIRE |
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