Double-Strand DNA Breaks Induced by Paracyclophane Gold(I) Complexes
| Autor: | Sebastian Bestgen, Beate Köberle, Martina Austeri, Thomas Wiesner, Stefan Bräse, Ute Schepers, Jan Paradies, Peter W. Roesky, Martina Falk, Carmen Seidl, Andreas Zimmer |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
Coordination sphere
Cell Survival Phosphines DNA damage Stereochemistry Molecular Conformation Apoptosis Crystallography X-Ray Ligands 010402 general chemistry 01 natural sciences Catalysis Histones Metal HeLa chemistry.chemical_compound Coordination Complexes Ethers Cyclic Animals Humans Moiety DNA Breaks Double-Stranded Phosphorylation Cytotoxicity Zebrafish biology 010405 organic chemistry Ligand Organic Chemistry General Chemistry HCT116 Cells biology.organism_classification 0104 chemical sciences chemistry Larva visual_art MCF-7 Cells visual_art.visual_art_medium Gold Tetrahydrothiophene HeLa Cells |
| Zdroj: | Chemistry - A European Journal. 23:6315-6322 |
| ISSN: | 0947-6539 |
| DOI: | 10.1002/chem.201605237 |
| Popis: | Gold(I) complexes of ClickPhos [2.2]paracyclophane ligands were synthesized in excellent yields and fully characterized by spectroscopic methods as well as X-ray crystallography. The complexes exhibit a rigid ligand backbone and a triazolyl moiety and were systematically studied with respect to their cytotoxic properties. In combination with the ionic complex [(GemPhos)Au(tht)][ClO4 ] (tht=tetrahydrothiophene), in which the gold(I) atom exhibits a distorted trigonal coordination sphere of two phosphines and a labile tht ligand, their efficiency in cytotoxicity was investigated in HeLa, MCF7, and HCT116 cells as well as in a zebrafish model. Their cytotoxicity and their mechanisms of action are different and involve apoptosis, necrosis, and DNA damage. The compounds presented herein are potent metal-based cytostatics displaying LD50 values from 3.5-38 μm in different tumor cell lines and induce double-strand DNA breaks (DSB) as shown by H2AX phosphorylation (γH2AX) at foci of DSBs. |
| Databáze: | OpenAIRE |
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