Polypyridyl-Based Copper Phenanthrene Complexes: Combining Stability with Enhanced DNA Recognition
| Autor: | John Colleran, Nicoló Zuin Fantoni, Sinéad O'Carroll, Chryssostomos Chatgilialoglu, Suainibhe Kelly, Anna Banasiak, Martin Clynes, Georgia Menounou, Andrew Kellett, George Mitrikas, Sandra Roche, Vickie McKee, Marios G. Krokidis, Zara Molphy |
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| Rok vydání: | 2020 |
| Předmět: |
DNA damage
DNA repair Stereochemistry Intercalation (chemistry) 010402 general chemistry Crystallography X-Ray 01 natural sciences Catalysis chemistry.chemical_compound Coordination Complexes Cell Line Tumor Organometallic Compounds Humans A-DNA 010405 organic chemistry Chemistry fungi Organic Chemistry Electron Spin Resonance Spectroscopy General Chemistry DNA Phenanthrenes Ligand (biochemistry) 0104 chemical sciences Pancreatic Neoplasms electrochemistry copper Hydroxyl radical Amine gas treating Copper EPR spectroscopy DNA Damage Phenanthrolines |
| Zdroj: | Fantoni, N Z, Molphy, Z, O'Carroll, S, Menounou, G, Mitrikas, G, Krokidis, M G, Chatgilialoglu, C, Colleran, J, Banasiak, A, Clynes, M, Roche, S, Kelly, S, McKee, V & Kellett, A 2021, ' Polypyridyl-Based Copper Phenanthrene Complexes : Combining Stability with Enhanced DNA Recognition ', Chemistry-A European Journal, vol. 27, no. 3, pp. 971-983 . https://doi.org/10.1002/chem.202001996 |
| ISSN: | 1521-3765 |
| Popis: | We report a series of copper(II) artificial metallo-nucleases (AMNs) and demonstrate their DNA damaging properties and in-vitro cytotoxicity against human-derived pancreatic cancer cells. The compounds combine a tris-chelating polypyridyl ligand, di-(2-pycolyl)amine (DPA), and a DNA intercalating phenanthrene unit. Their general formula is Cu-DPA-N,N' (where N,N'=1,10-phenanthroline (Phen), dipyridoquinoxaline (DPQ) or dipyridophenazine (DPPZ)). Characterisation was achieved by X-ray crystallography and continuous-wave EPR (cw-EPR), hyperfine sublevel correlation (HYSCORE) and Davies electron-nuclear double resonance (ENDOR) spectroscopies. The presence of the DPA ligand enhances solution stability and facilitates enhanced DNA recognition with apparent binding constants (Kapp) rising from 105 to 107 m−1 with increasing extent of planar phenanthrene. Cu-DPA-DPPZ, the complex with greatest DNA binding and intercalation effects, recognises the minor groove of guanine–cytosine (G-C) rich sequences. Oxidative DNA damage also occurs in the minor groove and can be inhibited by superoxide and hydroxyl radical trapping agents. The complexes, particularly Cu-DPA-DPPZ, display promising anticancer activity against human pancreatic tumour cells with in-vitro results surpassing the clinical platinum(II) drug oxaliplatin. |
| Databáze: | OpenAIRE |
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