Double-strand DNA breaks induced by Paracyclophane Gold(I) Complexes
- Authors
- Roesky, P.W., Bestgen, S., Seidl, C., Wiesner, T., Zimmer, A., Falk, M., Köberle, B., Austeri, M., Paradies, J., Bräse, S., Schepers, U.
- ID
- ZDB-PUB-170206-9
- Date
- 2017
- Source
- Chemistry (Weinheim an der Bergstrasse, Germany) 23(26): 6315-6322 (Journal)
- Registered Authors
- Keywords
- gold, paracyclophane, cytotoxicity, phosphine, tumor
- MeSH Terms
-
- Animals
- Apoptosis/drug effects
- Cell Survival/drug effects
- Coordination Complexes/chemical synthesis
- Coordination Complexes/chemistry*
- Coordination Complexes/toxicity
- Crystallography, X-Ray
- DNA Breaks, Double-Stranded/drug effects
- Ethers, Cyclic/chemistry
- Gold/chemistry*
- HCT116 Cells
- HeLa Cells
- Histones/metabolism
- Humans
- Larva/drug effects
- Larva/physiology
- Ligands
- MCF-7 Cells
- Molecular Conformation
- Phosphines/chemistry
- Phosphorylation/drug effects
- Zebrafish/growth & development
- PubMed
- 28156042 Full text @ Chemistry
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.