Premium
Double‐Strand DNA Breaks Induced by Paracyclophane Gold(I) Complexes
Author(s) -
Bestgen Sebastian,
Seidl Carmen,
Wiesner Thomas,
Zimmer Andreas,
Falk Martina,
Köberle Beate,
Austeri Martina,
Paradies Jan,
Bräse Stefan,
Schepers Ute,
Roesky Peter W.
Publication year - 2017
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201605237
Subject(s) - cytotoxicity , chemistry , hela , ligand (biochemistry) , dna , stereochemistry , moiety , coordination sphere , crystallography , in vitro , biochemistry , crystal structure , receptor
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)][ClO 4 ] (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 LD 50 values from 3.5–38 μ m in different tumor cell lines and induce double‐strand DNA breaks (DSB) as shown by H2AX phosphorylation (γH2AX) at foci of DSBs.